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Amyloid-β mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse

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Abstract

Alzheimer's disease (AD) is traditionally considered as a brain disorder featured by amyloid-β (Aβ) deposition. The current study on whether pathological changes of AD extend to the enteric nervous system (ENS) is still in its infancy. In this study, we found enteric Aβ deposition, intestinal dysfunction, and colonic inflammation in the young APP/PS1 mice. Moreover, these mice exhibited cholinergic and nitrergic signaling pathways damages and enteric neuronal loss. Our data show that Aβ42 treatment remarkably affected the gene expression of cultured myenteric neurons and the spontaneous contraction of intestinal smooth muscles. The intra-colon administration of Aβ42 induced ENS dysfunction, brain gliosis, and β-amyloidosis-like changes in the wild-type mice. Our results suggest that ENS mirrors the neuropathology observed in AD brains, and intestinal pathological changes may represent the prodromal events, which contribute to brain pathology in AD. In summary, our findings provide new opportunities for AD early diagnosis and prevention.

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All data generated or analyzed during this study are included in this published article (and its supplementary information files).

References

  1. Cummings J, Lee G, Zhong K, Fonseca J, Taghva K (2021) Alzheimer’s disease drug development pipeline: 2021. Alzheimers Dement (N Y) 7:e12179

    PubMed  Google Scholar 

  2. Wang J, Gu BJ, Masters CL, Wang YJ (2017) A systemic view of Alzheimer disease—insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol 13:612–623

    CAS  PubMed  Google Scholar 

  3. Roher AE, Esh CL, Kokjohn TA, Castaño EM, Van Vickle GD, Kalback WM, Patton RL, Luehrs DC, Daugs ID, Kuo YM et al (2009) Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimers Dement 5:18–29

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Sun HL, Chen SH, Yu ZY, Cheng Y, Tian DY, Fan DY, He CY, Wang J, Sun PY, Chen Y et al (2021) Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits. Mol Psychiatry 26:5568–5577

    CAS  PubMed  Google Scholar 

  5. Fung TC, Olson CA, Hsiao EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20:145–155

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Niesler B, Kuerten S, Demir IE, Schäfer KH (2021) Disorders of the enteric nervous system—a holistic view. Nat Rev Gastroenterol Hepatol 18:393–410

    PubMed  Google Scholar 

  7. Sohrabi M, Pecoraro HL, Combs CK (2021) Gut Inflammation induced by dextran sulfate sodium exacerbates amyloid-β plaque deposition in the AppNL-G-F mouse model of Alzheimer’s disease. J Alzheimers Dis 79:1235–1255

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen C, Ahn EH, Kang SS, Liu X, Alam A, Ye K (2020) Gut dysbiosis contributes to amyloid pathology, associated with C/EBPβ/AEP signaling activation in Alzheimer’s disease mouse model. Sci Adv 6:eaba0466

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu SC, Cao ZS, Chang KM, Juang JL (2017) Intestinal microbial dysbiosis aggravates the progression of Alzheimer’s disease in Drosophila. Nat Commun 8:24

    PubMed  PubMed Central  Google Scholar 

  10. Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, Kim DK, Kim HJ, Choi H, Hyun DW et al (2020) Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut 69:283–294

    CAS  PubMed  Google Scholar 

  11. Chalazonitis A, Rao M (2018) Enteric nervous system manifestations of neurodegenerative disease. Brain Res 1693:207–213

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Schneider S, Wright CM, Heuckeroth RO (2019) Unexpected roles for the second brain: enteric nervous system as master regulator of bowel function. Annu Rev Physiol 81:235–259

    PubMed  Google Scholar 

  13. Wang L, Fleming SM, Chesselet M-F, Taché Y (2008) Abnormal colonic motility in mice overexpressing human wild-type α-synuclein. NeuroReport 19:873

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang L, Magen I, Yuan PQ, Subramaniam SR, Richter F, Chesselet MF, Taché Y (2012) Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation. Neurogastroenterol Motil 24:e425–e436

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kim S, Kwon S-H, Kam T-I, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA (2019) Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease. Neuron 103:627-641.e627

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang X, Hu X, Yang Y, Takata T, Sakurai T (2016) Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res 1643:1–9

    CAS  PubMed  Google Scholar 

  17. Puig KL, Combs CK (2013) Expression and function of APP and its metabolites outside the central nervous system. Exp Gerontol 48:608–611

    CAS  PubMed  Google Scholar 

  18. Puig KL, Lutz BM, Urquhart SA, Rebel AA, Zhou X, Manocha GD, Sens M, Tuteja AK, Foster NL, Combs CK (2015) Overexpression of mutant amyloid-β protein precursor and presenilin 1 modulates enteric nervous system. J Alzheimers Dis 44:1263–1278

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Puig KL, Brose SA, Zhou X, Sens MA, Combs GF, Jensen MD, Golovko MY, Combs CK (2017) Amyloid precursor protein modulates macrophage phenotype and diet-dependent weight gain. Sci Rep 7:43725

    PubMed  PubMed Central  Google Scholar 

  20. Puig KL, Manocha GD, Combs CK (2015) Amyloid precursor protein mediated changes in intestinal epithelial phenotype in vitro. PLoS One 10:e0119534

    PubMed  PubMed Central  Google Scholar 

  21. Cabal A, Alonso-Cortina V, Gonzalez-Vazquez LO, Naves FJ, Del Valle ME, Vega JA (1995) beta-Amyloid precursor protein (beta APP) in human gut with special reference to the enteric nervous system. Brain Res Bull 38:417–423

    CAS  PubMed  Google Scholar 

  22. Vojtechova I, Machacek T, Kristofikova Z, Stuchlik A, Petrasek T (2022) Infectious origin of Alzheimer’s disease: amyloid beta as a component of brain antimicrobial immunity. PLoS Pathog 18:e1010929

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Li B, He Y, Ma J, Huang P, Du J, Cao L, Wang Y, Xiao Q, Tang H, Chen S (2019) Mild cognitive impairment has similar alterations as Alzheimer’s disease in gut microbiota. Alzheimers Dement 15:1357–1366

    PubMed  Google Scholar 

  24. Zhao L, Lin S, Bales KR, Gelfanova V, Koger D, Delong C, Hale J, Liu F, Hunter JM, Paul SM (2009) Macrophage-mediated degradation of beta-amyloid via an apolipoprotein E isoform-dependent mechanism. J Neurosci 29:3603–3612

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Welikovitch LA, Do Carmo S, Maglóczky Z, Malcolm JC, Lőke J, Klein WL, Freund T, Cuello AC (2020) Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain. Proc Natl Acad Sci USA 117:6844–6854

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Bayer TA, Wirths O (2010) Intracellular accumulation of amyloid-Beta—a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease. Front Aging Neurosci 2:8

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Khodabakhsh P, Bazrgar M, Dargahi L, Mohagheghi F, Asgari Taei A, Parvardeh S, Ahmadiani A (2021) Does Alzheimer’s disease stem in the gastrointestinal system? Life Sci 287:120088

    CAS  PubMed  Google Scholar 

  28. Sanders KM, Koh SD, Ro S, Ward SM (2012) Regulation of gastrointestinal motility—insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol 9:633–645

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Sanders KM, Ward SM (2019) Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract. Br J Pharmacol 176:212–227

    CAS  PubMed  Google Scholar 

  30. El-Yazbi AF, Cho WJ, Cena J, Schulz R, Daniel EE (2008) Smooth muscle NOS, colocalized with caveolin-1, modulates contraction in mouse small intestine. J Cell Mol Med 12:1404–1415

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Beck K, Friebe A, Voussen B (2018) Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells influences circular smooth muscle contractility in murine colon. Neurogastroenterol Motil 30:e13300

    CAS  PubMed  Google Scholar 

  32. Bódi N, Szalai Z, Bagyánszki M (2019) Nitrergic enteric neurons in health and disease-focus on animal models. Int J Mol Sci 20:2003

    PubMed  PubMed Central  Google Scholar 

  33. Iwasaki M, Akiba Y, Kaunitz JD (2019) Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system. F1000Res. https://doi.org/10.12688/f1000research.18039.1

    Article  PubMed  PubMed Central  Google Scholar 

  34. Anitha M, Vijay-Kumar M, Sitaraman SV, Gewirtz AT, Srinivasan S (2012) Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling. Gastroenterology 143:1006-1016.e4

    CAS  PubMed  Google Scholar 

  35. Caputi V, Marsilio I, Cerantola S, Roozfarakh M, Lante I, Galuppini F, Rugge M, Napoli E, Giulivi C, Orso G et al (2017) Toll-like receptor 4 modulates small intestine neuromuscular function through nitrergic and purinergic pathways. Front Pharmacol 8:350

    PubMed  PubMed Central  Google Scholar 

  36. Ye L, Li G, Goebel A, Raju AV, Kong F, Lv Y, Li K, Zhu Y, Raja S, He P et al (2020) Caspase-11-mediated enteric neuronal pyroptosis underlies Western diet-induced colonic dysmotility. J Clin Investig 130:3621–3636

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Heanue TA, Pachnis V (2011) Prospective identification and isolation of enteric nervous system progenitors using Sox2. Stem Cells 29:128–140

    CAS  PubMed  Google Scholar 

  38. Kulkarni S, Micci MA, Leser J, Shin C, Tang SC, Fu YY, Liu L, Li Q, Saha M, Li C et al (2017) Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc Natl Acad Sci USA 114:E3709–E3718

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Kesavardhana S, Malireddi RKS, Kanneganti TD (2020) Caspases in cell death, inflammation, and pyroptosis. Annu Rev Immunol 38:567–595

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Han XJ, Hu YY, Yang ZJ, Jiang LP, Shi SL, Li YR, Guo MY, Wu HL, Wan YY (2017) Amyloid β-42 induces neuronal apoptosis by targeting mitochondria. Mol Med Rep 16:4521–4528

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhan X, Stamova B, Sharp FR (2018) Lipopolysaccharide associates with amyloid plaques, neurons and oligodendrocytes in Alzheimer’s disease brain: a review. Front Aging Neurosci 10:42

    PubMed  PubMed Central  Google Scholar 

  42. Brown GC (2010) Nitric oxide and neuronal death. Nitric Oxide 23:153–165

    CAS  PubMed  Google Scholar 

  43. Ghasemi M, Mayasi Y, Hannoun A, Eslami SM, Carandang R (2018) Nitric oxide and mitochondrial function in neurological diseases. Neuroscience 376:48–71

    CAS  PubMed  Google Scholar 

  44. Delgado M, Varela N, Gonzalez-Rey E (2008) Vasoactive intestinal peptide protects against beta-amyloid-induced neurodegeneration by inhibiting microglia activation at multiple levels. Glia 56:1091–1103

    PubMed  Google Scholar 

  45. Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M (2010) Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 330:980–982

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang XM, Xiong K, Cai Y, Cai H, Luo XG, Feng JC, Clough RW, Patrylo PR, Struble RG, Yan XX (2010) Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex. Eur J Neurosci 31:710–721

    PubMed  PubMed Central  Google Scholar 

  47. Bero AW, Yan P, Roh JH, Cirrito JR, Stewart FR, Raichle ME, Lee JM, Holtzman DM (2011) Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat Neurosci 14:750–756

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Saiz-Sanchez D, Ubeda-Bañon I, De la Rosa-Prieto C, Martinez-Marcos A (2012) Differential expression of interneuron populations and correlation with amyloid-β deposition in the olfactory cortex of an AβPP/PS1 transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 31:113–129

    CAS  PubMed  Google Scholar 

  49. Rao M, Gershon MD (2016) The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 13:517–528

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Brooks AJ, Rowse G, Ryder A, Peach EJ, Corfe BM, Lobo AJ (2016) Systematic review: psychological morbidity in young people with inflammatory bowel disease - risk factors and impacts. Aliment Pharmacol Ther 44:3–15

    CAS  PubMed  Google Scholar 

  51. Custodia A, Ouro A, Romaus-Sanjurjo D, Pías-Peleteiro JM, de Vries HE, Castillo J, Sobrino T (2021) Endothelial progenitor cells and vascular alterations in Alzheimer’s disease. Front Aging Neurosci 13:811210

    CAS  PubMed  Google Scholar 

  52. Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, Lü Y, Cai M, Zhu C, Tan YL et al (2018) Gut microbiota is altered in patients with Alzheimer’s disease. J Alzheimers Dis 63:1337–1346

    CAS  PubMed  Google Scholar 

  53. Feng J, Dong L, Zhang J, Han X, Tang S, Song L, Cong L, Wang X, Wang Y, Du Y (2018) Unique expression pattern of KIBRA in the enteric nervous system of APP/PS1 mice. Neurosci Lett 675:41–47

    CAS  PubMed  Google Scholar 

  54. Manocha GD, Floden AM, Miller NM, Smith AJ, Nagamoto-Combs K, Saito T, Saido TC, Combs CK (2019) Temporal progression of Alzheimer’s disease in brains and intestines of transgenic mice. Neurobiol Aging 81:166–176

    PubMed  PubMed Central  Google Scholar 

  55. Li JW, Zong Y, Cao XP, Tan L, Tan L (2018) Microglial priming in Alzheimer’s disease. Ann Transl Med 6:176

    PubMed  PubMed Central  Google Scholar 

  56. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM et al (2014) NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–1059

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, Lamkanfi M, Kanneganti TD (2012) NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488:389–393

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Stoye NM, Dos Santos Guilherme M, Endres K (2020) Alzheimer’s disease in the gut-Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player. FASEB J 34:11883–11899

    CAS  PubMed  Google Scholar 

  59. Sohrabi M, Sahu B, Kaur H, Hasler WA, Prakash A, Combs CK (2022) Gastrointestinal changes and Alzheimer’s disease. Curr Alzheimer Res 19:335–350

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Furness JB, Stebbing MJ (2018) The first brain: species comparisons and evolutionary implications for the enteric and central nervous systems. Neurogastroenterol Motil. https://doi.org/10.1111/nmo.13234

    Article  PubMed  Google Scholar 

  61. Chen C, Zhou Y, Wang H, Alam A, Kang SS, Ahn EH, Liu X, Jia J, Ye K (2021) Gut inflammation triggers C/EBPβ/δ-secretase-dependent gut-to-brain propagation of Aβ and Tau fibrils in Alzheimer’s disease. EMBO J 40:e106320

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Pellegrini C, Daniele S, Antonioli L, Benvenuti L, D’Antongiovanni V, Piccarducci R, Pietrobono D, Citi V, Piragine E, Flori L et al (2020) Prodromal intestinal events in Alzheimer’s disease (AD): colonic dysmotility and inflammation are associated with enteric AD-related protein deposition. Int J Mol Sci 21:3523

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, Khachaturian AS, Vergallo A, Cavedo E, Snyder PJ et al (2018) The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 141:1917–1933

    PubMed  PubMed Central  Google Scholar 

  64. Delvalle NM, Fried DE, Rivera-Lopez G, Gaudette L, Gulbransen BD (2018) Cholinergic activation of enteric glia is a physiological mechanism that contributes to the regulation of gastrointestinal motility. Am J Physiol Gastrointest Liver Physiol 315:G473–G483

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Han X, Tang S, Dong L, Song L, Dong Y, Wang Y, Du Y (2017) Loss of nitrergic and cholinergic neurons in the enteric nervous system of APP/PS1 transgenic mouse model. Neurosci Lett 642:59–65

    CAS  PubMed  Google Scholar 

  66. Reiserer RS, Harrison FE, Syverud DC, McDonald MP (2007) Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer’s disease. Genes Brain Behav 6:54–65

    CAS  PubMed  Google Scholar 

  67. Sadowski M, Pankiewicz J, Scholtzova H, Ji Y, Quartermain D, Jensen CH, Duff K, Nixon RA, Gruen RJ, Wisniewski T (2004) Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice. J Neuropathol Exp Neurol 63:418–428

    CAS  PubMed  Google Scholar 

  68. Zhang Y, Geng R, Tu Q (2021) Gut microbial involvement in Alzheimer’s disease pathogenesis. Aging (Albany NY) 13:13359–13371

    CAS  PubMed  Google Scholar 

  69. Sun Y, Sommerville NR, Liu JYH, Ngan MP, Poon D, Ponomarev ED, Lu Z, Kung JSC, Rudd JA (2020) Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer’s disease pathology. J Physiol 598:4209–4223

    CAS  PubMed  Google Scholar 

  70. Brun P, Giron MC, Qesari M, Porzionato A, Caputi V, Zoppellaro C, Banzato S, Grillo AR, Spagnol L, De Caro R et al (2013) Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145:1323–1333

    CAS  PubMed  Google Scholar 

  71. Caputi V, Marsilio I, Filpa V, Cerantola S, Orso G, Bistoletti M, Paccagnella N, De Martin S, Montopoli M, Dall’Acqua S et al (2017) Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice. Br J Pharmacol 174:3623–3639

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Smith TH, Ngwainmbi J, Grider JR, Dewey WL, Akbarali HI (2013) An in-vitro preparation of isolated enteric neurons and glia from the myenteric plexus of the adult mouse. J Vis Exp 78:50688

    Google Scholar 

  73. Hou TT, Yang HY, Wang W, Wu QQ, Tian YR, Jia JP (2018) Sulforaphane inhibits the generation of amyloid-β oligomer and promotes spatial learning and memory in Alzheimer’s disease (PS1V97L) transgenic mice. J Alzheimers Dis 62:1803–1813

    PubMed  Google Scholar 

  74. Dorey E, Bamji-Mirza M, Najem D, Li Y, Liu H, Callaghan D, Walker D, Lue LF, Stanimirovic D, Zhang W (2017) Apolipoprotein E isoforms differentially regulate Alzheimer’s disease and amyloid-β-induced inflammatory response in vivo and in vitro. J Alzheimers Dis 57:1265–1279

    CAS  PubMed  Google Scholar 

  75. Li M, Liu E, Zhou Q, Li S, Wang X, Liu Y, Wang L, Sun D, Ye J, Gao Y et al (2018) TRPC1 null exacerbates memory deficit and apoptosis induced by amyloid-β. J Alzheimers Dis 63:761–772

    CAS  PubMed  Google Scholar 

  76. Chen S, Jia J (2020) Tenuifolin attenuates amyloid-β42-induced neuroinflammation in microglia through the NF-κB signaling pathway. J Alzheimers Dis 76:195–205

    CAS  PubMed  Google Scholar 

  77. Fa M, Orozco IJ, Francis YI, Saeed F, Gong Y, Arancio O (2010) Preparation of oligomeric beta-amyloid 1–42 and induction of synaptic plasticity impairment on hippocampal slices. J Vis Exp 41:1884

    Google Scholar 

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Acknowledgements

The authors acknowledge Dr. Liping Zhu and technician Shaohua Zhang (School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology) for excellent technical assistance.

Funding

This work was supported by the National Natural Science Foundation of China (grants 31721002, 81920208014, and 31930051 to YL, 32200795 to HL).

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  1. Guoqiang Liu and Quntao Yu are co-first authors.

Authors and Affiliations

  1. Medical College, Hubei University for Nationalities, Enshi, 445000, Hubei, China

    Guoqiang Liu

  2. Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 4030030, China

    Quntao Yu, Houze Zhu, Bo Tan, Hongyan Yu, Xinyan Li & Youming Lu

  3. Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China

    Quntao Yu, Houze Zhu, Bo Tan, Hongyan Yu, Xinyan Li, Youming Lu & Hao Li

  4. Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Youming Lu & Hao Li

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Contributions

GL, YL, and HL designed the studies and wrote the paper. GL and QY performed the major experiments. HZ, BT, HY, XL, and HL carried out the microscopic imaging, data collection and analysis, and mouse feeding. All authors reviewed and revised the manuscript, especially the authors HZ and HL made significant contributions in the process of paper revision.

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Correspondence to Youming Lu or Hao Li.

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Animal experimental procedures were conducted following the institutional guidelines and the Animal Care and Use Committee of the animal core facility at Huazhong University of Science and Technology, Wuhan, China.

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Liu, G., Yu, Q., Zhu, H. et al. Amyloid-β mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse. Cell. Mol. Life Sci. 80, 351 (2023). https://doi.org/10.1007/s00018-023-04948-9

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