{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:50:43Z","timestamp":1789404643567,"version":"build-2803163510"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>Background: Substantial evidence from recent research suggests an influential and underappreciated force in Alzheimer\u2019s disease (AD) pathogenesis: the pathological signals originate from outside the brain. Pathogenic bacteria produce amyloid-like proteins \u201ccurli\u201d that form biofilms and show functional similarities to human amyloid-\u03b2 (A\u03b2). These proteins may contribute to neurological disease progression via signaling cascade from the gut to the brain. Objective: We propose that curli causes neuroendocrine activation from the gut to brain that promotes central A\u03b2 pathology. Methods: PGP9.5 and TLR2 levels in response to curli in the lumen of Tg2576 AD mice were analyzed by immunohistochemical and qRT-PCR analysis. Western blot and human 3D in vitro enteroids culture systems were also used. 16S rRNA gene sequencing was used to investigate bacterial dysbiosis. Results: We found significant increase in bacterial-amyloid curli with elevated TLR2 at the mRNA level in the pre- and symptomatic Tg-AD gut compared to littermate WT controls. This data associates with increased gram-positive bacterial colonization in the ileum of the symptomatic AD mice. We found fundamental evidence for vagus nerve activation in response to bacterial curli. Neuroendocrine marker PGP9.5 was significantly elevated in the gut epithelium of symptomatic AD mice, and this was colocalized with increased TLR2 expression. Enteroids, 3D-human ileal mini-gut monolayer in vitro model system also revealed increase levels of TLR2 upon stimulation with purified bacterial curli fibrils. Conclusion: These findings reveal the importance of pathological changes within the gut-vagus-brain signaling in response to luminal bacterial amyloid that might play a vital role in central A\u03b2 pathogenesis seen in the AD brain.<\/jats:p>","DOI":"10.3233\/jad-220106","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T11:23:32Z","timestamp":1651836212000},"page":"191-205","source":"Crossref","is-referenced-by-count":27,"title":["Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer\u2019s Disease Mice with Central Amyloid-\u03b2 Pathology"],"prefix":"10.1177","volume":"88","author":[{"given":"Tushar K.","family":"Das","sequence":"first","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Blasco-Conesa","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Korf","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedram","family":"Honarpisheh","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, 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