{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:22:08Z","timestamp":1790623328461,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK121272\u201001A1"],"award-info":[{"award-number":["R01 DK121272\u201001A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK121272\u20103S1"],"award-info":[{"award-number":["R01DK121272\u20103S1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Gastrointestinal (GI) microbiome and gut\u2010brain axis are associated with the progression and pathology of Alzheimer's disease (AD). Amyloid deposition is thought to be a driver of AD, causing synaptic dysfunction and neuronal death in the brain. Chronic constipation is a common gastrointestinal (GI) dysmotility in AD patients, which impacts patient outcomes and quality of life. It is unknown if enteric amyloidosis disrupts myenteric neuron function and causes GI dysmotility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Untreated male and female APP\/PS1 (a transgenic murine model of brain amyloidosis) and sex\u2010matched control mice were followed until 12\u2009months of age. A separate cohort of mice was treated with a vehicle or the beta\u2010secretase (BACE1) inhibitor, lanabecestat, starting at 5\u2009months of age until 7\u2009months. GI motility was assessed in all mice by measuring whole GI transit in\u00a0vivo. Propulsive colonic motility and GI smooth muscle contractions were measured ex\u00a0vivo. At 7 or 12\u2009months old, amyloidosis in the brain and myenteric plexus was determined by immunohistochemistry or ELISA; the myenteric neural density, including the cholinergic and nitrergic neurons, was evaluated by immune staining and RT\u2010PCR; expression of pro\u2010inflammatory factors in the GI wall was assessed by RT\u2010PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>By 7\u2009months of age, male and female APP\/PS1 mice developed abundant amyloid plaques in the brain. Aged untreated male APP\/PS1 mice also demonstrated A\u03b2 deposition in the colonic myenteric ganglia, which was associated with increased fecal output and faster whole GI transit starting at 4\u20137\u2009months old, but vehicle\u2010 and lanabecestat\u2010treated male APP\/PS1 mice had similar GI motility to their non\u2010genetic controls until 7\u2009months old. None of the female APP\/PS1 mice showed GI dysmotility or myenteric amyloidosis. Two months of lanabecestat treatment effectively reduced amyloid plaque burden in the brains of female APP\/PS1 mice but not in male APP\/PS1 mice. Treatment with lanabecestat did not affect myenteric A\u03b2 intensity or GI motility in all APP\/PS1 mice. All APP\/PS1 mice did not show myenteric neuronal degeneration or inflammation until 12\u2009months old.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>APP\/PS1 mice do not recapitulate myenteric amyloidosis persistently and lack the phenotype of constipation observed in human AD patients; these mice should not be considered an adequate murine model for studying the role of myenteric amyloidosis in GI dysmotility. An adequate animal model with myenteric amyloidosis is required for further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70056","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T14:45:54Z","timestamp":1746197154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Studying the Role of Myenteric Amyloidosis in Gastrointestinal Dysmotility and Enteric Neural Dysfunction Using\n                    <scp>APP<\/scp>\n                    \/\n                    <scp>PS1<\/scp>\n                    Mice\u2014Is It an Adequate Animal Model?"],"prefix":"10.1111","volume":"37","author":[{"given":"Roxanne","family":"Fernandes","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Masino","sequence":"additional","affiliation":[{"name":"The Neuroscience Program Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Flood","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Lansdell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikitha","family":"Srikrishna","sequence":"additional","affiliation":[{"name":"Professorial Assistantship Program Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Mui","sequence":"additional","affiliation":[{"name":"Sparrow Health System Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Dorrance","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7882-5596","authenticated-orcid":false,"given":"James J.","family":"Galligan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; 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