{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:26:43Z","timestamp":1792801603302,"version":"4.5.0"},"reference-count":70,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Amyloid-\u03b2 (A\u03b2) is generated from amyloid-\u03b2 protein precursor (A\u03b2PP) via secretase enzymes. While A\u03b2PP processing and its localization are well understood, the function of A\u03b2PP is largely unknown. A\u03b2PP has been shown to localize to mitochondria, but the consequence of this is not understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We examined the consequences of modulating mitochondrial A\u03b2PP content on mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured mitochondrial A\u03b2PP localization in postmortem human brain from non-demented and AD subjects. To understand the effects of mitochondrial localization of A\u03b2PP on mitochondria, we leveraged A\u03b2PP constructs with increased (D23A) or decreased (3 M) mitochondrial localization compared to a wild-type (WT) construct. We measured mitochondrial function including dynamics and mitophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed increased A\u03b2PP mitochondrial localization in postmortem brain of sporadic AD subjects. Increased or decreased mitochondrial A\u03b2PP content led to reduced electron transport chain (ETC) activities, reduced ATP levels, increased mitochondrial superoxide production, hyperpolarized mitochondrial membrane potential, and increased mitochondrial calcium content. Reduced mitochondrial A\u03b2PP content reduced mitophagy flux, while increased mitochondrial A\u03b2PP content increased mitophagy flux. Increased or decreased mitochondrial A\u03b2PP content reduced mitochondrial biogenesis. We identified interactions between A\u03b2PP and mitophagy\/autophagy proteins. We next examined if a specific motif in A\u03b2PP was responsible for alterations in mitochondrial function and mitophagy. Mitophagy flux was inhibited with expression of \u0394CT A\u03b2PP, suggesting a role for the C-terminus of A\u03b2PP in mitophagy induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, these findings highlight a critical role of A\u03b2PP in mitochondrial physiology. Alterations to A\u03b2PP mitochondrial content can lead to mitochondrial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251360243","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T08:02:12Z","timestamp":1752739332000},"page":"277-293","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Amyloid-\u03b2 protein precursor modulates mitophagy and mitochondrial function through its cellular localization"],"prefix":"10.1177","volume":"107","author":[{"given":"Taylor A","family":"Strope","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA"},{"name":"University of Kansas Alzheimer's Disease Research Center, Kansas City, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Troutwine","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center, Kansas City, KS, USA"},{"name":"Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany M","family":"Hauger","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center, Kansas City, KS, USA"},{"name":"Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith P","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center, Kansas City, KS, USA"},{"name":"Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 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