{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:01:31Z","timestamp":1793642491677,"version":"4.5.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"\n Alzheimer\u2019s disease (AD) is characterized by impaired protein homeostasis leading to amyloid-\u03b2 peptide (A\u03b2) amyloidosis. Amyloid precursor protein (APP) knock-in mice exhibit robust A\u03b2 pathology, providing possibilities to determine its effect on protein homeostasis including autophagy. Here we compared human AD postmortem brain tissue with brains from two different types of\n App<\/jats:italic>\n knock-in mice,\n App<\/jats:italic>\n \n NL<\/jats:italic>\n \u2013\n F<\/jats:italic>\n <\/jats:sup>\n and\n App<\/jats:italic>\n \n NL<\/jats:italic>\n \u2013\n G<\/jats:italic>\n \u2013\n F<\/jats:italic>\n <\/jats:sup>\n mice, exhibiting AD-like pathology. In AD postmortem brains, p62 levels are increased and p62-positive staining is detected in neurons, including potential axonal beadings, as well as in the vasculature and in corpora amylacea. Interestingly, p62 is also increased in the neurons in 12-month-old\n App<\/jats:italic>\n \n NL<\/jats:italic>\n \u2013\n G<\/jats:italic>\n \u2013\n F<\/jats:italic>\n <\/jats:sup>\n mice. In brain homogenates from 12-month-old\n App<\/jats:italic>\n \n NL<\/jats:italic>\n \u2013\n G<\/jats:italic>\n \u2013\n F<\/jats:italic>\n <\/jats:sup>\n mice, both p62 and light chain 3 (LC3)-II levels are increased as compared to wildtype (WT) mice, indicating inhibited autophagy. Double immunostaining for LC3 and A\u03b2 revealed LC3-positive puncta in hippocampus of 24-month-old\n App<\/jats:italic>\n \n NL<\/jats:italic>\n \u2013\n F<\/jats:italic>\n <\/jats:sup>\n mice around the A\u03b2 plaques which was subsequently identified by electron microscopy imaging as an accumulation of autophagic vacuoles in dystrophic neurites around the A\u03b2 plaques. Taken together, autophagy is impaired in\n App<\/jats:italic>\n knock-in mice upon increased A\u03b2 pathology, indicating that\n App<\/jats:italic>\n knock-in mouse models provide a platform for understanding the correlation between A\u03b2 and autophagy.\n <\/jats:p>","DOI":"10.3389\/fnagi.2022.878303","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T01:37:10Z","timestamp":1652924230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Autophagy Impairment in App Knock-in Alzheimer\u2019s Model Mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Richeng","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Shimozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Tambaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Abelein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Winblad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"Bogdanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41598-019-57143-x","article-title":"High-yield production of Amyloid-\u03b2 peptide enabled by a customized spider silk domain.","volume":"10","author":"Abelein","year":"2020","journal-title":"Sci. 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