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Research Paper

Gut-derived β-amyloid: Likely a centerpiece of the gut–brain axis contributing to Alzheimer’s pathogenesis

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Article: 2167172 | Received 19 Jul 2022, Accepted 03 Jan 2023, Published online: 22 Jan 2023

References

  • Haque RU, Levey AI. Alzheimer’s disease: a clinical perspective and future nonhuman primate research opportunities. Proc Natl Acad Sci U S A. 2019;116 (52):26224–19. doi:10.1073/pnas.1912954116.
  • Hardy J. Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci. 1997;20:154–159. doi:10.1016/S0166-2236(96)01030-2.
  • Organization WH. Dementia. World Health Organization. Last updated June 1, 2022, Accessed on June 1, 2022. https://wwwwhoint/news-room/fact-sheets/detail/dementia
  • Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ (Clinical Research Ed). 2015;350:h369.
  • DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14:32. doi:10.1186/s13024-019-0333-5.
  • Esang M, Gupta M. Aducanumab as a novel treatment for Alzheimer’s disease: a decade of hope, controversies, and the future. Cureus. 2021;13:e17591. doi:10.7759/cureus.17591.
  • 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. doi:10.1016/j.lfs.2020.118627.
  • Kang YJ, Diep YN, Tran M, Cho H. Therapeutic targeting strategies for early- to late-staged Alzheimer’s disease. Int J Mol Sci. 2020;22:21.
  • Gorevic PD, Goñi F, Pons-Estel B, Alvarez F, Peress NS, Frangione B. Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer’s disease: immunohistological studies. J Neuropathol Exp Neurol. 1986;45:647–664. doi:10.1097/00005072-198611000-00004.
  • Trejo-Lopez JA, Yachnis AT, Prokop S. Neuropathology of Alzheimer’s disease. ASENT. 2022;19:173–185.
  • Rajmohan R, Reddy PH. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. JAD. 2017;57:975–999. doi:10.3233/JAD-160612.
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Sci (New York, NY). 2002;297:353–356. doi:10.1126/science.1072994.
  • Cheng Y, Tian DY, Wang YJ. Peripheral clearance of brain-derived Aβ in Alzheimer’s disease: pathophysiology and therapeutic perspectives. Transl Neurodegener. 2020;9:16. doi:10.1186/s40035-020-00195-1.
  • Schupf N, Tang MX, Fukuyama H, Manly J, Andrews H, Mehta P. Peripheral Abeta subspecies as risk biomarkers of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2008; 105(37):14052–14057. doi:10.1073/pnas.0805902105.
  • Zlokovic BV, Martel CL, Mackic JB, Matsubara E, Wisniewski T, McComb JG, Frangione B, Ghiso J. Brain uptake of circulating apolipoproteins J and E complexed to Alzheimer’s amyloid beta. Biochem Biophys Res Commun. 1994;205:1431–1437. doi:10.1006/bbrc.1994.2825.
  • Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11:457–470. doi:10.1038/nrneurol.2015.119.
  • Chen C, Zhou Y, Wang H, Alam A, Kang SS, Ahn EH, Liu X, Jia J, Ye K. Gut inflammation triggers C/EBPβ/δ-secretase-dependent gut-to-brain propagation of Aβ and Tau fibrils in Alzheimer’s disease. EMBO J. 2021;40:e106320. doi:10.15252/embj.2020106320.
  • Sun Y, Sommerville NR, Liu JYH, Ngan MP, Poon D, Ponomarev ED, Lu Z, Kung JSC, Rudd JA. Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer’s disease pathology. J Physiol. 2020;598:4209–4223. doi:10.1113/JP279919.
  • Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20:145–155. doi:10.1038/nn.4476.
  • Willyard C. How gut microbes could drive brain disorders. Nature. 2021;590:22–25. doi:10.1038/d41586-021-00260-3.
  • Shabbir U, Arshad MS, Sameen A, Oh DH. Nutrients. Crosstalk between Gut and Brain in Alzheimer's Disease: The Role of Gut Microbiota Modulation Strategies. 2021;13(2):690. doi:10.3390/nu13020690.
  • 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;57:5026–5043. doi:10.1007/s12035-020-02073-3.
  • Romanenko M, Kholin V, Koliada A, Vaiserman A. Nutrition, gut microbiota, and Alzheimer’s disease. Front Psych. 2021;12:712673. doi:10.3389/fpsyt.2021.712673.
  • Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7:13537. doi:10.1038/s41598-017-13601-y.
  • Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, Neher JJ, Fåk F, Jucker M, Lasser T, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep. 2017;7:41802. doi:10.1038/srep41802.
  • Askarova S, Umbayev B, Masoud AR, Kaiyrlykyzy A, Safarova Y, Tsoy A, Olzhayev F, Kushugulova A. The links between the gut microbiome, aging, modern lifestyle and Alzheimer’s disease. Front Cell Infect Microbiol. 2020;10:104. doi:10.3389/fcimb.2020.00104.
  • Wu YF, Lee WF, Salamanca E, Yao WL, Su JN, Wang SY. Oral microbiota changes in elderly patients, an indicator of Alzheimer’s disease. Int J Environ Res Public Health. 2021;19(1):18. doi:10.3390/ijerph19010018.
  • Shen L, Liu L, Ji HF. Alzheimer’s disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. JAD. 2017;56:385–390. doi:10.3233/JAD-160884.
  • Bäuerl C, Collado MC, Diaz Cuevas A, Viña J, Pérez Martínez G. Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer’s disease during lifespan. Lett Appl Microbiol. 2018;66:464–471. doi:10.1111/lam.12882.
  • Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, Kim DK, Kim HJ, Choi H, Hyun D-W, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2020;69:283–294. doi:10.1136/gutjnl-2018-317431.
  • Honarpisheh P, Reynolds CR, Blasco Conesa MP, Moruno Manchon JF, Putluri N, Bhattacharjee MB. Dysregulated gut homeostasis observed prior to the accumulation of the brain amyloid-β in Tg2576 mice. Int J Mol Sci. 2020;22(1):21. doi:10.3390/ijms22010021.
  • Zhang L, Wang Y, Xiayu X, Shi C, Chen W, Song N. Altered gut microbiota in a mouse model of Alzheimer’s disease. JAD. 2017;60:1241–1257. doi:10.3233/JAD-170020.
  • Kang JN, Sun ZF, Li XY, Zhang XD, Jin ZX, Zhang C, Zhang Y, Wang H-Y, Huang -N-N, Jiang J-H, et al. Alterations in gut microbiota are related to metabolite profiles in spinal cord injury. Neural Regen Res. 2023;18:1076–1083. doi:10.4103/1673-5374.355769.
  • Tortora SC, Bodiwala VM, Quinn A, Martello LA, Vignesh S. Microbiome and colorectal carcinogenesis: linked mechanisms and racial differences. World J Gastrointest Oncol. 2022;14:375–395. doi:10.4251/wjgo.v14.i2.375.
  • Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J . Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A. 2019;116(26):12672–12677.
  • Raftar SKA, Ashrafian F, Abdollahiyan S, Yadegar A, Moradi HR, Masoumi M. The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD/CCL4-induced murine model of liver injury. Sci Rep. 2022;12:2453. doi:10.1038/s41598-022-06414-1.
  • Li H, Xie J, Guo X, Yang G, Cai B, Liu J. Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses Gut microbes. 2022;14:2127456.
  • Lam V, Takechi R, Hackett MJ, Francis R, Bynevelt M, Celliers LM, Nesbit M, Mamsa S, Arfuso F, Das S, et al. Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. PLoS Biol. 2021;19:e3001358. doi:10.1371/journal.pbio.3001358.
  • Bu XL, Xiang Y, Jin WS, Wang J, Shen LL, Huang ZL, Zhang K, Liu Y-H, Zeng F, Liu J-H, et al. Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Mol Psychiatry. 2018;23:1948–1956. doi:10.1038/mp.2017.204.
  • Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, et al. Transneuronal propagation of pathologic α-Synuclein from the gut to the brain models Parkinson’s disease. Neuron. 2019;103(627–41.e7). doi:10.1016/j.neuron.2019.05.035.
  • Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil. 2019;25:48–60. doi:10.5056/jnm18087.
  • Galloway S, Takechi R, Pallebage-Gamarallage MM, Dhaliwal SS, Mamo JC. Amyloid-beta colocalizes with apolipoprotein B in absorptive cells of the small intestine. Lipids Health Dis. 2009;8:46. doi:10.1186/1476-511X-8-46.
  • Pallebage-Gamarallage MM, Galloway S, Takechi R, Dhaliwal S, Mamo JC. Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding. Lipids. 2012;47:27–34. doi:10.1007/s11745-011-3595-4.
  • Galloway S, Jian L, Johnsen R, Chew S, Mamo JC. beta-amyloid or its precursor protein is found in epithelial cells of the small intestine and is stimulated by high-fat feeding. J Nutr Biochem. 2007;18:279–284. doi:10.1016/j.jnutbio.2006.07.003.
  • Kumar DK, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, Lefkowitz A, McColl G, Goldstein LE, Tanzi RE, et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci Trans Med. 2016;8:340ra72. doi:10.1126/scitranslmed.aaf1059.
  • Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, et al. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PloS one. 2010;5:e9505. doi:10.1371/journal.pone.0009505.
  • Benilova I, Karran E, De Strooper B. The toxic Aβ oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci. 2012;15:349–357. doi:10.1038/nn.3028.
  • Kwak SS, Washicosky KJ, Brand E, von Maydell D, Aronson J, Kim S, Capen DE, Cetinbas M, Sadreyev R, Ning S, et al. Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease. Nat Commun. 2020;11:1377. doi:10.1038/s41467-020-15120-3.
  • Arotcarena ML, Dovero S, Prigent A, Bourdenx M, Camus S, Porras G, Thiolat M-L, Tasselli M, Aubert P, Kruse N, et al. Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates. Brain J Neuro. 2020;143:1462–1475. doi:10.1093/brain/awaa096.
  • Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG, Reichmann H, et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PloS one. 2010;5:e8762. doi:10.1371/journal.pone.0008762.
  • Ulusoy A, Rusconi R, Pérez-Revuelta BI, Musgrove RE, Helwig M, Winzen-Reichert B, Monte DAD. Caudo-rostral brain spreading of α-synuclein through vagal connections. EMBO Mol Med. 2013;5:1119–1127. doi:10.1002/emmm.201302475.
  • Wu S, Liu X, Jiang R, Yan X, Ling Z. Roles and mechanisms of gut microbiota in patients with Alzheimer’s disease. Front Aging Neurosci. 2021;13:650047. doi:10.3389/fnagi.2021.650047.
  • Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, Lü Y, Cai M, Zhu C, Tan Y-L, et al. Gut microbiota is altered in patients with Alzheimer’s disease. JAD. 2018;63:1337–1346. doi:10.3233/JAD-180176.
  • Choi J, Hur TY, Hong Y. Influence of altered gut microbiota composition on aging and aging-related diseases. J Lifestyle Med. 2018;8:1–7. doi:10.15280/jlm.2018.8.1.1.
  • Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–68. doi:10.1016/j.neurobiolaging.2016.08.019.
  • Brandscheid C, Schuck F, Reinhardt S, Schäfer KH, Pietrzik CU, Grimm M, Hartmann T, Schwiertz A, Endres K. Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer’s mouse model. JAD. 2017;56:775–788. doi:10.3233/JAD-160926.
  • Osadchiy V, Martin CR, Mayer EA. The gut-brain axis and the microbiome: mechanisms and clinical implications. Clin Gastroenterol. 2019;17:322–332. doi:10.1016/j.cgh.2018.10.002.
  • Gershon MD, Margolis KG. The gut, its microbiome, and the brain: connections and communications. J Clin Invest . 2021;131:e143768. doi:10.1172/JCI143768
  • Morais LH, HLt S, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2021;19:241–255. doi:10.1038/s41579-020-00460-0.
  • Martin CR, Osadchiy V, Kalani A, Mayer EA. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol. 2018;6:133–148. doi:10.1016/j.jcmgh.2018.04.003.
  • Boehme M, Guzzetta KE, Bastiaanssen TFS, van de Wouw M, Moloney GM, Gual-Grau A, Spichak S, Olavarría-Ramírez L, Fitzgerald P, Morillas E, et al. Microbiota from young mice counteracts selective age-associated behavioral deficits. Nat Aging. 2021;1:666–676. doi:10.1038/s43587-021-00093-9.
  • Wu Q, Wang B, Li QF, Zhang X, Ntim M, Wu XF, Li N, Zhu -D-D, Jiang R, Yang J-Y, et al. SRC-1 knockout exerts no effect on Amyloid β deposition in APP/PS1 mice. Front Aging Neurosci. 2020;12:145. doi:10.3389/fnagi.2020.00145.
  • Zhang B, Wang HE, Bai YM, Tsai SJ, Su TP, Chen TJ, Wang Y-P, Chen M-H. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut. 2021;70:85–91. doi:10.1136/gutjnl-2020-320789.
  • Charisis S, Ntanasi E, Yannakoulia M, Anastasiou CA, Kosmidis MH, Dardiotis E, Gargalionis AN, Patas K, Chatzipanagiotou S, Mourtzinos I, et al. Diet inflammatory index and dementia incidence: a population-based study. Neurology. 2021;97:e2381–e91. doi:10.1212/WNL.0000000000012973.
  • Foshati S, Akhlaghi M, Babajafari S. The effect of pro-/synbiotic supplementation on the brain-derived neurotrophic factor: a systematic review and meta-analysis of randomized controlled trials. Food Funct. 2022;13:8754–8765. doi:10.1039/D2FO01330D.
  • Maezawa I, Hong HS, Wu HC, Battina SK, Rana S, Iwamoto T, Radke GA, Pettersson E, Martin GM, Hua DH, et al. A novel tricyclic pyrone compound ameliorates cell death associated with intracellular amyloid-beta oligomeric complexes. J Neurochem. 2006;98:57–67. doi:10.1111/j.1471-4159.2006.03862.x.
  • Tao R, Wang N, Shen T, Tan Y, Ren Y, Wei W, Liao M, Tan D, Tang C, Xu N, et al. High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer’s disease. Theranostics. 2022;12:2549–2559. doi:10.7150/thno.68743.