Long JM, Holtzman DM. Alzheimer Disease: an update on pathobiology and treatment strategies. Cell. 2019;179(2):312–39.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–90.
Knopman DS, Amieva H, Petersen RC, Chetelat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33.
Graff-Radford J, Yong KXX, Apostolova LG, Bouwman FH, Carrillo M, Dickerson BC, et al. New insights into atypical Alzheimer’s disease in the era of biomarkers. Lancet Neurol. 2021;20(3):222–34.
Di Paolo G, Kim TW. Linking lipids to Alzheimer’s disease: cholesterol and beyond. Nat Rev Neurosci. 2011;12(5):284–96.
Sastry PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res. 1985;24(2):69–176.
Schonfeld P, Reiser G. Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain. J Cereb Blood Flow Metab. 2013;33(10):1493–9.
Sezgin E, Levental I, Mayor S, Eggeling C. The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol. 2017;18(6):361–74.
Yoon JH, Seo Y, Jo YS, Lee S, Cho E, Cazenave-Gassiot A, et al. Brain lipidomics: from functional landscape to clinical significance. Sci Adv. 2022;8(37):eadc9317.
Sebastiao AM, Colino-Oliveira M, Assaife-Lopes N, Dias RB, Ribeiro JA. Lipid rafts, synaptic transmission and plasticity: impact in age-related neurodegenerative diseases. Neuropharmacology. 2013;64:97–107.
Kao YC, Ho PC, Tu YK, Jou IM, Tsai KJ. Lipids and Alzheimer’s Disease. Int J Mol Sci. 2020;21(4).
Cardoso S, Carvalho C, Correia SC, Seica RM, Moreira PI. Alzheimer’s Disease: from mitochondrial perturbations to mitochondrial medicine. Brain Pathol. 2016;26(5):632–47.
Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic Biol Med. 2016;100:108–22.
Hamilton LK, Dufresne M, Joppe SE, Petryszyn S, Aumont A, Calon F, et al. Aberrant lipid metabolism in the Forebrain Niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer’s Disease. Cell Stem Cell. 2015;17(4):397–411.
Ferre-Gonzalez L, Lloret A, Chafer-Pericas C. Systematic review of brain and blood lipidomics in Alzheimer’s disease mouse models. Prog Lipid Res. 2023;90:101223.
Teitsdottir UD, Halldorsson S, Rolfsson O, Lund SH, Jonsdottir MK, Snaedal J, et al. Cerebrospinal fluid C18 Ceramide Associates with markers of Alzheimer’s disease and inflammation at the pre- and early stages of Dementia. J Alzheimers Dis. 2021;81(1):231–44.
Mielke MM, Bandaru VV, Haughey NJ, Xia J, Fried LP, Yasar S, et al. Serum ceramides increase the risk of Alzheimer disease: the women’s Health and Aging Study II. Neurology. 2012;79(7):633–41.
Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:k2179.
Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877–2013.
Martin CR, Osadchiy V, Kalani A, Mayer EA. The brain-gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 2018;6(2):133–48.
Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55–71.
Lynch SV, Pedersen O. The human intestinal microbiome in Health and Disease. N Engl J Med. 2016;375(24):2369–79.
Long-Smith C, O’Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota-Gut-Brain Axis: New Therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2020;60:477–502.
Fulling C, Dinan TG, Cryan JF. Gut microbe to Brain Signaling: what happens in Vagus. Neuron. 2019;101(6):998–1002.
Sun BL, Li WW, Wang J, Xu YL, Sun HL, Tian DY, et al. Gut microbiota alteration and its time course in a Tauopathy Mouse Model. J Alzheimers Dis. 2019;70(2):399–412.
Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, et al. Gut microbiota is altered in patients with Alzheimer’s Disease. J Alzheimers Dis. 2018;63(4):1337–46.
Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–8.
Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell Mol Life Sci. 2017;74(20):3769–87.
Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7(1):13537.
Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, et al. Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav Immun. 2019;80:633–43.
Ferreiro AL, Choi J, Ryou J, Newcomer EP, Thompson R, Bollinger RM, et al. Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Sci Transl Med. 2023;15(700):eabo2984.
Wang YR, Liang CR, Heng T, Zhang T, Hu XT, Long Y, et al. Circulating antibodies to Helicobacter pylori are associated with biomarkers of neurodegeneration in cognitively intact adults. Asian J Psychiatr. 2023;86:103680.
Shen L, Liu L, Ji HF. Alzheimer’s disease histological and behavioral manifestations in transgenic mice correlate with specific gut Microbiome State. J Alzheimers Dis. 2017;56(1):385–90.
Brandscheid C, Schuck F, Reinhardt S, Schafer KH, Pietrzik CU, Grimm M, et al. Altered gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer’s mouse model. J Alzheimers Dis. 2017;56(2):775–88.
Chandra S, Sisodia SS, Vassar RJ. The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored. Mol Neurodegener. 2023;18(1):9.
Mezo C, Dokalis N, Mossad O, Staszewski O, Neuber J, Yilmaz B, et al. Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer’s disease. Acta Neuropathol Commun. 2020;8(1):119.
Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, et al. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Sci Rep. 2016;6:30028.
Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep. 2017;7:41802.
Zhang Y, Shen Y, Liufu N, Liu L, Li W, Shi Z, et al. Transmission of Alzheimer’s disease-associated microbiota dysbiosis and its impact on cognitive function: evidence from mice and patients. Mol Psychiatry. 2023;28(10):4421–37.
Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2020;69(2):283–94.
Simao DO, Vieira VS, Tosatti JAG, Gomes KB, Lipids. Gut Microbiota, and the Complex Relationship with Alzheimer’s Disease: A Narrative Review. Nutrients. 2023;15(21).
Cheng X, Tan Y, Li H, Huang J, Zhao D, Zhang Z, et al. Fecal 16S rRNA sequencing and multi-compartment metabolomics revealed gut microbiota and metabolites interactions in APP/PS1 mice. Comput Biol Med. 2022;151Pt A:106312.
Qian X, Hai W, Chen S, Zhang M, Jiang X, Tang H. Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice. Gut Microbes. 2023;15(2):2282790.
Mirzaei R, Bouzari B, Hosseini-Fard SR, Mazaheri M, Ahmadyousefi Y, Abdi M, et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed Pharmacother. 2021;139:111661.
Chen C, Liao J, Xia Y, Liu X, Jones R, Haran J, et al. Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut. 2022;71(11):2233–52.
Bonfili L, Cuccioloni M, Gong C, Cecarini V, Spina M, Zheng Y, et al. Gut microbiota modulation in Alzheimer’s disease: focus on lipid metabolism. Clin Nutr. 2022;41(3):698–708.
Lei E, Vacy K, Boon WC. Fatty acids and their therapeutic potential in neurological disorders. Neurochem Int. 2016;95:75–84.
Li X, Bi X, Wang S, Zhang Z, Li F, Zhao AZ. Therapeutic potential of omega-3 polyunsaturated fatty acids in Human Autoimmune diseases. Front Immunol. 2019;10:2241.
Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O’Brien R, et al. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: a nontargeted metabolomic study. PLoS Med. 2017;14(3):e1002266.
Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 2017;16(5):377–89.
El Shatshat A, Pham AT, Rao PPN. Interactions of polyunsaturated fatty acids with amyloid peptides Abeta40 and Abeta42. Arch Biochem Biophys. 2019;663:34–43.
Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA, et al. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2012;29(3):691–7.
Bogie JFJ, Haidar M, Kooij G, Hendriks JJA. Fatty acid metabolism in the progression and resolution of CNS disorders. Adv Drug Deliv Rev. 2020;159:198–213.
Yamashima T, Ota T, Mizukoshi E, Nakamura H, Yamamoto Y, Kikuchi M, et al. Intake of omega-6 polyunsaturated fatty acid-rich vegetable oils and risk of Lifestyle diseases. Adv Nutr. 2020;11(6):1489–509.
Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56(8):365–79.
Gustafson DR, Backman K, Scarmeas N, Stern Y, Manly JJ, Mayeux R, et al. Dietary fatty acids and risk of Alzheimer’s disease and related dementias: observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP). Alzheimers Dement. 2020;16(12):1638–49.
Howe AM, Burke S, O’Reilly ME, McGillicuddy FC, Costello DA. Palmitic acid and oleic acid differently modulate TLR2-Mediated inflammatory responses in Microglia and macrophages. Mol Neurobiol. 2022;59(4):2348–62.
Fraser T, Tayler H, Love S. Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer’s disease. Neurochem Res. 2010;35(3):503–13.
Flores-Leon M, Perez-Dominguez M, Gonzalez-Barrios R, Arias C. Palmitic Acid-Induced NAD(+) depletion is Associated with the reduced function of SIRT1 and increased expression of BACE1 in hippocampal neurons. Neurochem Res. 2019;44(7):1745–54.
Marwarha G, Claycombe-Larson K, Lund J, Ghribi O. Palmitate-Induced SREBP1 expression and activation underlies the increased BACE 1 activity and amyloid Beta Genesis. Mol Neurobiol. 2019;56(7):5256–69.
Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE, Small SA, et al. Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem. 2012;287(4):2678–88.
Diaz G, Lengele L, Sourdet S, Soriano G, de Souto Barreto P. Nutrients and amyloid beta status in the brain: a narrative review. Ageing Res Rev. 2022;81:101728.
Umeda T, Tomiyama T, Kitajima E, Idomoto T, Nomura S, Lambert MP, et al. Hypercholesterolemia accelerates intraneuronal accumulation of Abeta oligomers resulting in memory impairment in Alzheimer’s disease model mice. Life Sci. 2012;91(23–24):1169–76.
Bossaerts L, Cacace R, Van Broeckhoven C. The role of ATP-binding cassette subfamily A in the etiology of Alzheimer’s disease. Mol Neurodegener. 2022;17(1):31.
Wood WG, Li L, Muller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer’s disease: a debatable hypothesis. J Neurochem. 2014;129(4):559–72.
Silva T, Teixeira J, Remiao F, Borges F. Alzheimer’s disease, cholesterol, and statins: the junctions of important metabolic pathways. Angew Chem Int Ed Engl. 2013;52(4):1110–21.
van der Kant R, Langness VF, Herrera CM, Williams DA, Fong LK, Leestemaker Y, et al. Cholesterol metabolism is a Druggable Axis that independently regulates tau and amyloid-beta in iPSC-Derived Alzheimer’s disease neurons. Cell Stem Cell. 2019;24(3):363–75. e9.
Ooi KM, Vacy K, Boon WC. Fatty acids and beyond: Age and Alzheimer’s disease related changes in lipids reveal the neuro-nutraceutical potential of lipids in cognition. Neurochem Int. 2021;149:105143.
Gonzalez-Dominguez R, Garcia-Barrera T, Gomez-Ariza JL. Combination of metabolomic and phospholipid-profiling approaches for the study of Alzheimer’s disease. J Proteom. 2014;104:37–47.
Blusztajn JK, Slack BE. Accelerated breakdown of Phosphatidylcholine and Phosphatidylethanolamine is a predominant brain metabolic defect in Alzheimer’s Disease. J Alzheimers Dis. 2023;93(4):1285–9.
Varma VR, Oommen AM, Varma S, Casanova R, An Y, Andrews RM, et al. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: a targeted metabolomics study. PLoS Med. 2018;15(1):e1002482.
Rodriguez-Cuenca S, Pellegrinelli V, Campbell M, Oresic M, Vidal-Puig A. Sphingolipids and glycerophospholipids – the Ying and Yang of lipotoxicity in metabolic diseases. Prog Lipid Res. 2017;66:14–29.
Wood PL, Mankidy R, Ritchie S, Heath D, Wood JA, Flax J, et al. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale-cognitive scores in Alzheimer patients. J Psychiatry Neurosci. 2010;35(1):59–62.
Su XQ, Wang J, Sinclair AJ. Plasmalogens and Alzheimer’s disease: a review. Lipids Health Dis. 2019;18(1):100.
Dorninger F, Forss-Petter S, Berger J. From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system. FEBS Lett. 2017;591(18):2761–88.
Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968;9(5):570–9.
Bader Lange ML, Cenini G, Piroddi M, Abdul HM, Sultana R, Galli F, et al. Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease. Neurobiol Dis. 2008;29(3):456–64.
Kim HY, Huang BX, Spector AA. Phosphatidylserine in the brain: metabolism and function. Prog Lipid Res. 2014;56:1–18.
Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell. 2015;160(6):1061–71.
Scott-Hewitt N, Perrucci F, Morini R, Erreni M, Mahoney M, Witkowska A, et al. Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. EMBO J. 2020;39(16):e105380.
Popescu AS, Butler CA, Allendorf DH, Piers TM, Mallach A, Roewe J, et al. Alzheimer’s disease-associated R47H TREM2 increases, but wild-type TREM2 decreases, microglial phagocytosis of synaptosomes and neuronal loss. Glia. 2023;71(4):974–90.
Fracassi A, Marcatti M, Tumurbaatar B, Woltjer R, Moreno S, Taglialatela G. TREM2-induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer’s neuropathology. Brain Pathol. 2023;33(1):e13108.
Rueda-Carrasco J, Sokolova D, Lee SE, Childs T, Jurcakova N, Crowley G, et al. Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer’s disease models. EMBO J. 2023;42(19):e113246.
Jesko H, Stepien A, Lukiw WJ, Strosznajder RP. The Cross-talk between sphingolipids and insulin-like growth factor signaling: significance for aging and neurodegeneration. Mol Neurobiol. 2019;56(5):3501–21.
van Echten-Deckert G, Walter J. Sphingolipids: critical players in Alzheimer’s disease. Prog Lipid Res. 2012;51(4):378–93.
Xu J, Bankov G, Kim M, Wretlind A, Lord J, Green R, et al. Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer’s disease. Transl Neurodegener. 2020;9(1):36.
Crivelli SM, Giovagnoni C, Visseren L, Scheithauer AL, de Wit N, den Hoedt S, et al. Sphingolipids in Alzheimer’s disease, how can we target them? Adv Drug Deliv Rev. 2020;159:214–31.
Parveen F, Bender D, Law SH, Mishra VK, Chen CC, Ke LY. Role of ceramidases in Sphingolipid Metabolism and Human diseases. Cells. 2019;8(12).
Dinkins MB, Enasko J, Hernandez C, Wang G, Kong J, Helwa I, et al. Neutral Sphingomyelinase-2 Deficiency ameliorates Alzheimer’s Disease Pathology and improves cognition in the 5XFAD mouse. J Neurosci. 2016;36(33):8653–67.
Krautkramer KA, Fan J, Backhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol. 2021;19(2):77–94.
Wu L, Han Y, Zheng Z, Peng G, Liu P, Yue S et al. Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host-Microbe Interplay. Nutrients. 2021;13(1).
van der Hee B, Wells JM. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 2021;29(8):700–12.
Qian XH, Xie RY, Liu XL, Chen SD, Tang HD. Mechanisms of short-chain fatty acids derived from Gut Microbiota in Alzheimer’s Disease. Aging Dis. 2022;13(4):1252–66.
Liu J, Li H, Gong T, Chen W, Mao S, Kong Y, et al. Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer’s Disease via Upregulating GPR41 and inhibiting ERK/JNK/NF-kappaB. J Agric Food Chem. 2020;68(27):7152–61.
Hoyles L, Snelling T, Umlai UK, Nicholson JK, Carding SR, Glen RC, et al. Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier. Microbiome. 2018;6(1):55.
Govindarajan N, Agis-Balboa RC, Walter J, Sananbenesi F, Fischer A. Sodium butyrate improves memory function in an Alzheimer’s disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis. 2011;26(1):187–97.
Ge X, Zheng M, Hu M, Fang X, Geng D, Liu S et al. Butyrate ameliorates quinolinic acid-induced cognitive decline in obesity models. J Clin Invest. 2023;133(4).
Colombo AV, Sadler RK, Llovera G, Singh V, Roth S, Heindl S et al. Microbiota-derived short chain fatty acids modulate microglia and promote abeta plaque deposition. Elife. 2021;10.
Erny D, Dokalis N, Mezo C, Castoldi A, Mossad O, Staszewski O, et al. Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab. 2021;33(11):2260–76. e7.
Seo DO, O’Donnell D, Jain N, Ulrich JD, Herz J, Li Y, et al. ApoE isoform- and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy. Science. 2023;379(6628):eadd1236.
Zhou Y, Xie L, Schroder J, Schuster IS, Nakai M, Sun G, et al. Dietary Fiber and Microbiota Metabolite Receptors Enhance Cognition and alleviate Disease in the 5xFAD mouse model of Alzheimer’s Disease. J Neurosci. 2023;43(37):6460–75.
Spichak S, Bastiaanssen TFS, Berding K, Vlckova K, Clarke G, Dinan TG, et al. Mining microbes for mental health: determining the role of microbial metabolic pathways in human brain health and disease. Neurosci Biobehav Rev. 2021;125:698–761.
Connell E, Le Gall G, Pontifex MG, Sami S, Cryan JF, Clarke G, et al. Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia. Mol Neurodegener. 2022;17(1):43.
MahmoudianDehkordi S, Arnold M, Nho K, Ahmad S, Jia W, Xie G, et al. Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease-An emerging role for gut microbiome. Alzheimers Dement. 2019;15(1):76–92.
Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, et al. Metabolic Network Analysis reveals altered bile acid synthesis and metabolism in Alzheimer’s Disease. Cell Rep Med. 2020;1(8):100138.
Huang F, Pariante CM, Borsini A. From dried bear bile to molecular investigation: a systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Brain Behav Immun. 2022;99:132–46.
Dionisio PA, Amaral JD, Ribeiro MF, Lo AC, D’Hooge R, Rodrigues CM. Amyloid-beta pathology is attenuated by tauroursodeoxycholic acid treatment in APP/PS1 mice after disease onset. Neurobiol Aging. 2015;36(1):228–40.
Yanguas-Casas N, Barreda-Manso MA, Nieto-Sampedro M, Romero-Ramirez L. TUDCA: an agonist of the bile acid receptor GPBAR1/TGR5 with anti-inflammatory effects in Microglial cells. J Cell Physiol. 2017;232(8):2231–45.
Zangerolamo L, Vettorazzi JF, Rosa LRO, Carneiro EM, Barbosa HCL. The bile acid TUDCA and neurodegenerative disorders: an overview. Life Sci. 2021;272:119252.
Khalaf K, Tornese P, Cocco A, Albanese A. Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases. Transl Neurodegener. 2022;11(1):33.
Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016;87(22):2324–32.
Zhao Y, Cong L, Jaber V, Lukiw WJ. Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain. Front Immunol. 2017;8:1064.
Kim HS, Kim S, Shin SJ, Park YH, Nam Y, Kim CW, et al. Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications. Transl Neurodegener. 2021;10(1):49.
Brown GC. The endotoxin hypothesis of neurodegeneration. J Neuroinflammation. 2019;16(1):180.
Wu Z, Ni J, Liu Y, Teeling JL, Takayama F, Collcutt A, et al. Cathepsin B plays a critical role in inducing Alzheimer’s disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav Immun. 2017;65:350–61.
Erickson MA, Hartvigson PE, Morofuji Y, Owen JB, Butterfield DA, Banks WA. Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier. J Neuroinflammation. 2012;9:150.
Ye X, Zhu M, Che X, Wang H, Liang XJ, Wu C, et al. Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation. J Neuroinflammation. 2020;17(1):18.
Yao C, Liu X, Tang Y, Wang C, Duan C, Liu X, et al. Lipopolysaccharide induces inflammatory microglial activation through CD147-mediated matrix metalloproteinase expression. Environ Sci Pollut Res Int. 2023;30(12):35352–65.
Calvo-Rodriguez M, Garcia-Rodriguez C, Villalobos C, Nunez L. Role of toll like receptor 4 in Alzheimer’s Disease. Front Immunol. 2020;11:1588.
Miron J, Picard C, Frappier J, Dea D, Theroux L, Poirier J. TLR4 gene expression and pro-inflammatory cytokines in Alzheimer’s Disease and in response to hippocampal deafferentation in rodents. J Alzheimers Dis. 2018;63(4):1547–56.
Kim S, Chung H, Ngoc Mai H, Nam Y, Shin SJ, Park YH et al. Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease. Int J Mol Sci. 2020;21(12).
Izumi Y, Cashikar AG, Krishnan K, Paul SM, Covey DF, Mennerick SJ, et al. A proinflammatory stimulus disrupts hippocampal plasticity and learning via Microglial activation and 25-Hydroxycholesterol. J Neurosci. 2021;41(49):10054–64.
Wong MY, Lewis M, Doherty JJ, Shi Y, Cashikar AG, Amelianchik A, et al. 25-Hydroxycholesterol amplifies microglial IL-1beta production in an apoE isoform-dependent manner. J Neuroinflammation. 2020;17(1):192.
Cashikar AG, Toral-Rios D, Timm D, Romero J, Strickland M, Long JM, et al. Regulation of astrocyte lipid metabolism and ApoE secretionby the microglial oxysterol, 25-hydroxycholesterol. J Lipid Res. 2023;64(4):100350.
Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Transl Res. 2021;228:109–25.
Vogt NM, Romano KA, Darst BF, Engelman CD, Johnson SC, Carlsson CM, et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther. 2018;10(1):124.
Chen ML, Zhu XH, Ran L, Lang HD, Yi L, Mi MT. Trimethylamine-N-Oxide induces vascular inflammation by activating the NLRP3 Inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc. 2017;6(9).
Wilson A, McLean C, Kim RB. Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis. Curr Opin Lipidol. 2016;27(2):148–54.
Li D, Ke Y, Zhan R, Liu C, Zhao M, Zeng A, et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell. 2018;17(4):e12768.
Gao Q, Wang Y, Wang X, Fu S, Zhang X, Wang RT, et al. Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease. Aging. 2019;11(19):8642–63.
Li D, Yu S, Long Y, Shi A, Deng J, Ma Y, et al. Tryptophan metabolism: mechanism-oriented therapy for neurological and psychiatric disorders. Front Immunol. 2022;13:985378.
Agus A, Planchais J, Sokol H. Gut microbiota regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018;23(6):716–24.
Salminen A. Activation of aryl hydrocarbon receptor (AhR) in Alzheimer’s disease: role of tryptophan metabolites generated by gut host-microbiota. J Mol Med (Berl). 2023;101(3):201–22.
Ramprasath T, Han YM, Zhang D, Yu CJ, Zou MH. Tryptophan catabolism and inflammation: a Novel Therapeutic Target for aortic diseases. Front Immunol. 2021;12:731701.
Wang HC, Wong TH, Wang LT, Su HH, Yu HY, Wu AH, et al. Aryl hydrocarbon receptor signaling promotes ORMDL3-dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase. Cell Mol Immunol. 2019;16(10):783–90.
Majumder S, Kono M, Lee YT, Byrnes C, Li C, Tuymetova G, et al. A genome-wide CRISPR/Cas9 screen reveals that the aryl hydrocarbon receptor stimulates sphingolipid levels. J Biol Chem. 2020;295(13):4341–9.
Pappolla MA, Perry G, Fang X, Zagorski M, Sambamurti K, Poeggeler B. Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer’s disease. Neurobiol Dis. 2021;156:105403.
Sun J, Zhang Y, Kong Y, Ye T, Yu Q, Kumaran Satyanarayanan S, et al. Microbiota-derived metabolite indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice. Brain Behav Immun. 2022;106:76–88.
George N, Jawaid Akhtar M, Al Balushi KA, Alam Khan S. Rational drug design strategies for the development of promising multi-target directed indole hybrids as Anti-alzheimer agents. Bioorg Chem. 2022;127:105941.
Chen YC, Chiu YJ, Lin CH, Hsu WC, Wu JL, Huang CH, et al. Indole Compound NC009-1 augments APOE and TRKA in Alzheimer’s Disease Cell and Mouse models for Neuroprotection and Cognitive Improvement. J Alzheimers Dis. 2019;67(2):737–56.
van der Velpen V, Teav T, Gallart-Ayala H, Mehl F, Konz I, Clark C, et al. Systemic and central nervous system metabolic alterations in Alzheimer’s disease. Alzheimers Res Ther. 2019;11(1):93.
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019;51(3):414–30.
Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77(1):43–51.
Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54(4):412–36.
Picard C, Julien C, Frappier J, Miron J, Theroux L, Dea D, et al. Alterations in cholesterol metabolism-related genes in sporadic Alzheimer’s disease. Neurobiol Aging. 2018;66:180e1. e9.
Serrano-Pozo A, Das S, Hyman BT. APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021;20(1):68–80.
Raulin AC, Doss SV, Trottier ZA, Ikezu TC, Bu G, Liu CC. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Mol Neurodegener. 2022;17(1):72.
Martens YA, Zhao N, Liu CC, Kanekiyo T, Yang AJ, Goate AM, et al. ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias. Neuron. 2022;110(8):1304–17.
Koutsodendris N, Nelson MR, Rao A, Huang Y. Apolipoprotein E and Alzheimer’s Disease: findings, hypotheses, and potential mechanisms. Annu Rev Pathol. 2022;17:73–99.
Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Palsson E, et al. Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. JAMA Psychiatry. 2014;71(10):1183–91.
Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, Luo W, et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature. 2017;549(7673):523–7.
Davis AA, Inman CE, Wargel ZM, Dube U, Freeberg BM, Galluppi A et al. APOE genotype regulates pathology and disease progression in synucleinopathy. Sci Transl Med. 2020;12(529).
Tran TTT, Corsini S, Kellingray L, Hegarty C, Le Gall G, Narbad A, et al. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. FASEB J. 2019;33(7):8221–31.
Nunes AF, Amaral JD, Lo AC, Fonseca MB, Viana RJ, Callaerts-Vegh Z, et al. TUDCA, a bile acid, attenuates amyloid precursor protein processing and amyloid-beta deposition in APP/PS1 mice. Mol Neurobiol. 2012;45(3):440–54.
Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. TREM2 binds to Apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-Beta by Microglia. Neuron. 2016;91(2):328–40.
Filipello F, Morini R, Corradini I, Zerbi V, Canzi A, Michalski B, et al. The Microglial Innate Immune receptor TREM2 is required for synapse elimination and normal brain connectivity. Immunity. 2018;48(5):979–91. e8.
Zhou Y, Song WM, Andhey PS, Swain A, Levy T, Miller KR, et al. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease. Nat Med. 2020;26(1):131–42.
Ulland TK, Song WM, Huang SC, Ulrich JD, Sergushichev A, Beatty WL, et al. TREM2 maintains microglial metabolic fitness in Alzheimer’s Disease. Cell. 2017;170(4):649–63. e13.
Nugent AA, Lin K, van Lengerich B, Lianoglou S, Przybyla L, Davis SS, et al. TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron. 2020;105(5):837–54. e9.
Deczkowska A, Weiner A, Amit I. The Physiology, Pathology, and potential therapeutic applications of the TREM2 signaling pathway. Cell. 2020;181(6):1207–17.
Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, et al. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep. 2019;9(1):5790.
Wang Y, Lin Y, Wang L, Zhan H, Luo X, Zeng Y, et al. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice. Aging. 2020;12(20):20862–79.
Li H, Liu F, Jiang W, Wang K, Cao X, Zou J, et al. TREM2 ameliorates Lipopolysaccharide-Induced oxidative stress response and neuroinflammation by promoting Sirtuin3 in BV2 cells. Neurotox Res. 2022;40(1):56–65.
Li R, Zhang J, Wang Q, Cheng M, Lin B. TPM1 mediates inflammation downstream of TREM2 via the PKA/CREB signaling pathway. J Neuroinflammation. 2022;19(1):257.
Lewandowski CT, Laham MS, Thatcher GRJ. Remembering your A, B, C’s: Alzheimer’s disease and ABCA1. Acta Pharm Sin B. 2022;12(3):995–1018.
Nordestgaard LT, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Loss-of-function mutation in ABCA1 and risk of Alzheimer’s disease and cerebrovascular disease. Alzheimers Dement. 2015;11(12):1430–8.
Wahrle SE, Jiang H, Parsadanian M, Kim J, Li A, Knoten A, et al. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest. 2008;118(2):671–82.
Holstege H, Hulsman M, Charbonnier C, Grenier-Boley B, Quenez O, Grozeva D, et al. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease. Nat Genet. 2022;54(12):1786–94.
Du Y, Li X, Su C, Xi M, Zhang X, Jiang Z, et al. Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice. Br J Pharmacol. 2020;177(8):1754–72.
Mohammadi A, Najar AG, Yaghoobi MM, Jahani Y, Vahabzadeh Z. Trimethylamine-N-Oxide treatment induces changes in the ATP-Binding Cassette Transporter A1 and scavenger receptor A1 in murine macrophage J774A.1 cells. Inflammation. 2016;39(1):393–404.
Yang Y, Karampoor S, Mirzaei R, Borozdkin L, Zhu P. The interplay between microbial metabolites and macrophages in cardiovascular diseases: a comprehensive review. Int Immunopharmacol. 2023;121:110546.
Moulton MJ, Barish S, Ralhan I, Chang J, Goodman LD, Harland JG, et al. Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer’s disease-associated genes. Proc Natl Acad Sci U S A. 2021;118:52.
Steinberg S, Stefansson H, Jonsson T, Johannsdottir H, Ingason A, Helgason H, et al. Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease. Nat Genet. 2015;47(5):445–7.
Satoh K, Abe-Dohmae S, Yokoyama S, St George-Hyslop P, Fraser PE. ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. J Biol Chem. 2015;290(40):24152–65.
Aikawa T, Ren Y, Holm ML, Asmann YW, Alam A, Fitzgerald ML, et al. ABCA7 regulates brain fatty acid metabolism during LPS-Induced Acute inflammation. Front Neurosci. 2021;15:647974.
Wojtas AM, Kang SS, Olley BM, Gatherer M, Shinohara M, Lozano PA, et al. Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways. Proc Natl Acad Sci U S A. 2017;114(33):E6962–71.
Jun YK, Yoon HT, Kwon SH, Jo UH, Kim JE, Han YM, et al. Regulation of psoriasis, colitis, and the intestinal microbiota by clusterin. Sci Rep. 2023;13(1):15405.
Wang QJ, Shen YE, Wang X, Fu S, Zhang X, Zhang YN, et al. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. Aging. 2020;12(1):628–49.
Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89(3):331–40.
Shimano H, Sato R. SREBP-regulated lipid metabolism: convergent physiology – divergent pathophysiology. Nat Rev Endocrinol. 2017;13(12):710–30.
Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, et al. Osmotin reduced amyloid beta (abeta) burden by inhibiting SREBP2 expression in APP/PS1 mice. Mol Psychiatry. 2017;22(3):323.
Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, et al. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatry. 2017;22(3):407–16.
Vourakis M, Mayer G, Rousseau G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int J Mol Sci. 2021;22(15).
Jucker M, Walker LC. Alzheimer’s disease: from immunotherapy to immunoprevention. Cell. 2023;186(20):4260–70.
Zhang Y, Chen H, Li R, Sterling K, Song W. Amyloid beta-based therapy for Alzheimer’s disease: challenges, successes and future. Signal Transduct Target Ther. 2023;8(1):248.
Campos-Pena V, Pichardo-Rojas P, Sanchez-Barbosa T, Ortiz-Islas E, Rodriguez-Perez CE, Montes P et al. Amyloid beta, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer’s Disease. Int J Mol Sci. 2022;23(20).
Moll T, Marshall JNG, Soni N, Zhang S, Cooper-Knock J, Shaw PJ. Membrane lipid raft homeostasis is directly linked to neurodegeneration. Essays Biochem. 2021;65(7):999–1011.
Bode DC, Freeley M, Nield J, Palma M, Viles JH. Amyloid-beta oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy. J Biol Chem. 2019;294(19):7566–72.
Kiriyama Y, Nochi H. The biosynthesis, signaling, and neurological functions of bile acids. Biomolecules. 2019;9(6).
Liu S, Gao J, Zhu M, Liu K, Zhang HL. Gut microbiota and Dysbiosis in Alzheimer’s Disease: implications for Pathogenesis and treatment. Mol Neurobiol. 2020;57(12):5026–43.
Drummond E, Pires G, MacMurray C, Askenazi M, Nayak S, Bourdon M, et al. Phosphorylated tau interactome in the human Alzheimer’s disease brain. Brain. 2020;143(9):2803–17.
Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener. 2020;15(1):40.
Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc Natl Acad Sci U S A. 2021;118:33.
Xia Y, Xiao Y, Wang ZH, Liu X, Alam AM, Haran JP, et al. Bacteroides Fragilis in the gut microbiomes of Alzheimer’s disease activates microglia and triggers pathogenesis in neuronal C/EBPbeta transgenic mice. Nat Commun. 2023;14(1):5471.
Song X, Zhao Z, Zhao Y, Wang Z, Wang C, Yang G, et al. Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl(3) induced mouse model of Alzheimer’s disease via modulating gut microbiota and PI3K/Akt/GSK-3beta signaling pathway. Nutr Neurosci. 2022;25(12):2588–600.
Qian XH, Song XX, Liu XL, Chen SD, Tang HD. Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota. Ageing Res Rev. 2021;68:101317.
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21(3):383–421.
Bairamian D, Sha S, Rolhion N, Sokol H, Dorothee G, Lemere CA, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17(1):19.
Haran JP, Bhattarai SK, Foley SE, Dutta P, Ward DV, Bucci V et al. Alzheimer’s Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway. mBio. 2019;10(3).
Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–77.
Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586–97.
Dodiya HB, Lutz HL, Weigle IQ, Patel P, Michalkiewicz J, Roman-Santiago CJ et al. Gut microbiota-driven brain abeta amyloidosis in mice requires microglia. J Exp Med. 2022;219(1).
Chandra S, Di Meco A, Dodiya HB, Popovic J, Cuddy LK, Weigle IQ, et al. The gut microbiome regulates astrocyte reaction to Abeta amyloidosis through microglial dependent and independent mechanisms. Mol Neurodegener. 2023;18(1):45.
Minter MR, Hinterleitner R, Meisel M, Zhang C, Leone V, Zhang X, et al. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APP(SWE)/PS1(DeltaE9) murine model of Alzheimer’s disease. Sci Rep. 2017;7(1):10411.
Chen C, Ahn EH, Kang SS, Liu X, Alam A, Ye K. Gut dysbiosis contributes to amyloid pathology, associated with C/EBPbeta/AEP signaling activation in Alzheimer’s disease mouse model. Sci Adv. 2020;6(31):eaba0466.
Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363–83.
Shandilya S, Kumar S, Kumar Jha N, Kumar Kesari K, Ruokolainen J. Interplay of gut microbiota and oxidative stress: perspective on neurodegeneration and neuroprotection. J Adv Res. 2022;38:223–44.
Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):R453–62.
Fao L, Mota SI, Rego AC. Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases. Ageing Res Rev. 2019;54:100942.
Szentirmai E, Millican NS, Massie AR, Kapas L. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep. 2019;9(1):7035.
Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res. 2021;164:105314.
Chambers ES, Preston T, Frost G, Morrison DJ. Role of gut microbiota-generated short-chain fatty acids in metabolic and Cardiovascular Health. Curr Nutr Rep. 2018;7(4):198–206.
Sivandzade F, Prasad S, Bhalerao A, Cucullo L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches. Redox Biol. 2019;21:101059.
Seo EJ, Fischer N, Efferth T. Phytochemicals as inhibitors of NF-kappaB for treatment of Alzheimer’s disease. Pharmacol Res. 2018;129:262–73.
Wang L, Zhang X, Xiong X, Zhu H, Chen R, Zhang S et al. Nrf2 regulates oxidative stress and its role in cerebral ischemic stroke. Antioxid (Basel). 2022;11(12).
Kerr JS, Adriaanse BA, Greig NH, Mattson MP, Cader MZ, Bohr VA, et al. Mitophagy and Alzheimer’s Disease: Cellular and Molecular mechanisms. Trends Neurosci. 2017;40(3):151–66.
Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A, Gupta R. VDAC1, mitochondrial dysfunction, and Alzheimer’s disease. Pharmacol Res. 2018;131:87–101.
Yoo W, Zieba JK, Foegeding NJ, Torres TP, Shelton CD, Shealy NG, et al. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science. 2021;373(6556):813–8.
Mottawea W, Chiang CK, Muhlbauer M, Starr AE, Butcher J, Abujamel T, et al. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn’s disease. Nat Commun. 2016;7:13419.
Mossad O, Batut B, Yilmaz B, Dokalis N, Mezo C, Nent E, et al. Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N(6)-carboxymethyllysine. Nat Neurosci. 2022;25(3):295–305.
Wang C, Zheng D, Weng F, Jin Y, He L. Sodium butyrate ameliorates the cognitive impairment of Alzheimer’s disease by regulating the metabolism of astrocytes. Psychopharmacology. 2022;239(1):215–27.
Sharma VK, Mehta V, Singh TG. Alzheimer’s disorder: epigenetic connection and Associated Risk factors. Curr Neuropharmacol. 2020;18(8):740–53.
Nativio R, Lan Y, Donahue G, Sidoli S, Berson A, Srinivasan AR, et al. An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease. Nat Genet. 2020;52(10):1024–35.
Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science. 2010;328(5979):753–6.
Graff J, Rei D, Guan JS, Wang WY, Seo J, Hennig KM, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature. 2012;483(7388):222–6.
Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature. 2009;459(7243):55–60.
Lin Y, Lin A, Cai L, Huang W, Yan S, Wei Y, et al. ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease. Mol Neurodegener. 2023;18(1):47.
Kesika P, Suganthy N, Sivamaruthi BS, Chaiyasut C. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease. Life Sci. 2021;264:118627.
Bonfili L, Cecarini V, Gogoi O, Berardi S, Scarpona S, Angeletti M, et al. Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2020;87:35–43.
Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep. 2017;7(1):2426.
Bonfili L, Cecarini V, Cuccioloni M, Angeletti M, Berardi S, Scarpona S, et al. SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Mol Neurobiol. 2018;55(10):7987–8000.
Menden A, Hall D, Hahn-Townsend C, Broedlow CA, Joshi U, Pearson A, et al. Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer’s disease-like pathology in APP/PS1 mice. Sci Rep. 2022;12(1):4797.
Kaur H, Nagamoto-Combs K, Golovko S, Golovko MY, Klug MG, Combs CK. Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2020;92:114–34.
Abraham D, Feher J, Scuderi GL, Szabo D, Dobolyi A, Cservenak M, et al. Exercise and probiotics attenuate the development of Alzheimer’s disease in transgenic mice: role of microbiome. Exp Gerontol. 2019;115:122–31.
Shamsipour S, Sharifi G, Taghian F. An 8-Week Administration of Bifidobacterium bifidum and Lactobacillus plantarum combined with Exercise Training alleviates neurotoxicity of abeta and spatial learning via Acetylcholine in Alzheimer Rat Model. J Mol Neurosci. 2021;71(7):1495–505.
Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A Comprehensive Review on the role of the gut Microbiome in Human Neurological disorders. Clin Microbiol Rev. 2022;35(1):e0033820.
Zhang S, Lv S, Li Y, Wei D, Zhou X, Niu X, et al. Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice. Eur J Nutr. 2023;62(7):2991–3007.
Lee YS, Lai DM, Huang HJ, Lee-Chen GJ, Chang CH, Hsieh-Li HM, et al. Prebiotic lactulose ameliorates the cognitive deficit in Alzheimer’s Disease Mouse Model through Macroautophagy and chaperone-mediated autophagy pathways. J Agric Food Chem. 2021;69(8):2422–37.
Liu Q, Xi Y, Wang Q, Liu J, Li P, Meng X, et al. Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer’s disease mouse model via regulating the gut microbiota-brain axis. Brain Behav Immun. 2021;95:330–43.
Sun J, Xu J, Ling Y, Wang F, Gong T, Yang C, et al. Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice. Transl Psychiatry. 2019;9(1):189.
Kim N, Jeon SH, Ju IG, Gee MS, Do J, Oh MS, et al. Transplantation of gut microbiota derived from Alzheimer’s disease mouse model impairs memory function and neurogenesis in C57BL/6 mice. Brain Behav Immun. 2021;98:357–65.
Jin J, Xu Z, Zhang L, Zhang C, Zhao X, Mao Y, et al. Gut-derived beta-amyloid: likely a centerpiece of the gut-brain axis contributing to Alzheimer’s pathogenesis. Gut Microbes. 2023;15(1):2167172.
Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep. 2017;7(1):13510.
Lee HJ, Lee KE, Kim JK, Kim DH. Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice. Sci Rep. 2019;9(1):11814.
Wu Y, Niu X, Li P, Tong T, Wang Q, Zhang M, et al. Lactobacillaceae improve cognitive dysfunction via regulating gut microbiota and suppressing Abeta deposits and neuroinflammation in APP/PS1 mice. Arch Microbiol. 2023;205(4):118.
Cao J, Amakye WK, Qi C, Liu X, Ma J, Ren J. Bifidobacterium Lactis Probio-M8 regulates gut microbiota to alleviate Alzheimer’s disease in the APP/PS1 mouse model. Eur J Nutr. 2021;60(7):3757–69.
Sun J, Xu J, Yang B, Chen K, Kong Y, Fang N, et al. Effect of Clostridium butyricum against microglia-mediated neuroinflammation in Alzheimer’s Disease via regulating gut microbiota and metabolites Butyrate. Mol Nutr Food Res. 2020;64(2):e1900636.
Xin Y, Diling C, Jian Y, Ting L, Guoyan H, Hualun L, et al. Effects of oligosaccharides from Morinda Officinalis on Gut Microbiota and Metabolome of APP/PS1 transgenic mice. Front Neurol. 2018;9:412.
Shabbir U, Tyagi A, Elahi F, Aloo SO, Oh DH. The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer’s Disease. Antioxid (Basel). 2021;10(9).
Zhang J, Hao J, Liu R, Wu T, Liu R, Sui W, et al. Hawthorn flavonoid ameliorates cognitive deficit in mice with Alzheimer’s disease by increasing the levels of Bifidobacteriales in gut microbiota and docosapentaenoic acid in serum metabolites. Food Funct. 2022;13(23):12371–82.
Sun ZZ, Li XY, Wang S, Shen L, Ji HF. Bidirectional interactions between curcumin and gut microbiota in transgenic mice with Alzheimer’s disease. Appl Microbiol Biotechnol. 2020;104(8):3507–15.
Zhang J, Zheng Y, Luo Y, Du Y, Zhang X, Fu J. Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-kappaB pathways in BV2 cells. Mol Immunol. 2019;116:29–37.
Li J, Zhao R, Jiang Y, Xu Y, Zhao H, Lyu X, et al. Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia. Food Funct. 2020;11(2):1572–84.
Xu J, Chen HB, Li SL. Understanding the Molecular mechanisms of the interplay between Herbal Medicines and Gut Microbiota. Med Res Rev. 2017;37(5):1140–85.
Xu QQ, Su ZR, Yang W, Zhong M, Xian YF, Lin ZX. Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer’s disease via modulating neuropathology and gut microbiota through suppressing C/EBPbeta/AEP pathway. J Neuroinflammation. 2023;20(1):19.
Fu J, Li J, Sun Y, Liu S, Song F, Liu Z. In-depth investigation of the mechanisms of Schisandra chinensis polysaccharide mitigating Alzheimer’s disease rat via gut microbiota and feces metabolomics. Int J Biol Macromol. 2023;232:123488.
Wang Y, Wang M, Fan K, Li T, Yan T, Wu B, et al. Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide-induced animal model of Alzheimer’s disease. J Ethnopharmacol. 2018;217:98–106.
Xu M, Yang Y, Peng J, Zhang Y, Wu B, He B et al. Effects of Alpinae Oxyphyllae Fructus on microglial polarization in a LPS-induced BV2 cells model of neuroinflammation via TREM2. J Ethnopharmacol. 2023;302(Pt A):115914.
Shi K, Chen L, Chen L, Tan A, Xie G, Long Q, et al. Epimedii Folium and Curculiginis Rhizoma ameliorate lipopolysaccharides-induced cognitive impairment by regulating the TREM2 signaling pathway. J Ethnopharmacol. 2022;284:114766.
Sun Y, Zhang H, Liu R, Huang R, Zhang X, Zhou S, et al. Pyrolae herba alleviates cognitive impairment via hippocampal TREM2 signaling modulating neuroinflammation and neurogenesis in lipopolysaccharide-treated mice. J Ethnopharmacol. 2024;319(Pt 2):117214.
Kim J, Lee H, An J, Song Y, Lee CK, Kim K, et al. Alterations in gut microbiota by statin therapy and possible Intermediate effects on Hyperglycemia and Hyperlipidemia. Front Microbiol. 2019;10:1947.
Zahedi E, Sanaeierad A, Nikbakhtzadeh M, Roghani M, Zamani E. Simvastatin improves learning and memory impairment via gut-brain axis regulation in an ovariectomized/D-galactose Alzheimer’s rat model. Behav Brain Res. 2023;453:114611.
Daily JW, Kang S, Park S. Protection against Alzheimer’s disease by luteolin: role of brain glucose regulation, anti-inflammatory activity, and the gut microbiota-liver-brain axis. BioFactors. 2021;47(2):218–31.
Xu TC, Lv Y, Liu QY, Chen HS. Long-term atorvastatin improves cognitive decline by regulating gut function in naturally ageing rats. Immun Ageing. 2022;19(1):52.
Pellegrini C, Antonioli L, Calderone V, Colucci R, Fornai M, Blandizzi C. Microbiota-gut-brain axis in health and disease: is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications? Prog Neurobiol. 2020;191:101806.
Nagpal R, Neth BJ, Wang S, Craft S, Yadav H. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019;47:529–42.
Ma D, Wang AC, Parikh I, Green SJ, Hoffman JD, Chlipala G, et al. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci Rep. 2018;8(1):6670.
Wegierska AE, Charitos IA, Topi S, Potenza MA, Montagnani M, Santacroce L. The connection between Physical Exercise and Gut Microbiota: implications for competitive sports athletes. Sports Med. 2022;52(10):2355–69.
Dohnalova L, Lundgren P, Carty JRE, Goldstein N, Wenski SL, Nanudorn P, et al. A microbiome-dependent gut-brain pathway regulates motivation for exercise. Nature. 2022;612(7941):739–47.
Dalton A, Mermier C, Zuhl M. Exercise influence on the microbiome-gut-brain axis. Gut Microbes. 2019;10(5):555–68.
Du Z, Li Y, Li J, Zhou C, Li F, Yang X. Physical activity can improve cognition in patients with Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled trials. Clin Interv Aging. 2018;13:1593–603.
Gubert C, Kong G, Renoir T, Hannan AJ. Exercise, diet and stress as modulators of gut microbiota: implications for neurodegenerative diseases. Neurobiol Dis. 2020;134:104621.
Kang SS, Jeraldo PR, Kurti A, Miller ME, Cook MD, Whitlock K, et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol Neurodegener. 2014;9:36.
Yuan S, Yang J, Jian Y, Lei Y, Yao S, Hu Z, et al. Treadmill Exercise modulates intestinal microbes and suppresses LPS displacement to Alleviate Neuroinflammation in the brains of APP/PS1 mice. Nutrients. 2022;14:19.
Zhang Y, Wang G, Li R, Liu R, Yu Z, Zhang Z, et al. Trimethylamine N-oxide aggravated cognitive impairment from APP/PS1 mice and protective roles of voluntary exercise. Neurochem Int. 2023;162:105459.
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