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The rare familial mutations in APP and presenilin\u20101\/2, which sometimes drive increased amyloid \u03b2 (A\u03b2) production, may have unduly influenced Alzheimer's disease research. APP and its cleavage products play important roles in cellular and mitochondrial metabolism, but many studies focus solely on A\u03b2. Mitochondrial bioenergetic metabolism is essential for neuronal function, maintenance and survival, and multiple reports indicate mitochondrial abnormalities in patients with Alzheimer's disease. In this review, we focus on mitochondrial abnormalities reported in sporadic Alzheimer's disease patients and the role of full\u2010length APP and its non\u2010amyloidogenic fragments, particularly soluble APP\u03b1, on mitochondrial bioenergetic metabolism. We do not review the plethora of animal and <jats:italic>in vitro<\/jats:italic> studies using mutant APP\/presenilin constructs or experiments using exogenous A\u03b2. In doing so, we aim to invigorate research and discussion around non\u2010amyloidogenic APP processing products and the mechanisms linking mitochondria and complex neurodegenerative disorders such as sporadic Alzheimer's disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.18\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.18\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14554","type":"journal-article","created":{"date-parts":[[2018,11,24]],"date-time":"2018-11-24T16:09:25Z","timestamp":1543075765000},"page":"3464-3474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Amyloid precursor protein\u2010mediated mitochondrial regulation and Alzheimer's disease"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-5964","authenticated-orcid":false,"given":"M Isabel G","family":"Lopez Sanchez","sequence":"first","affiliation":[{"name":"Ophthalmology, Department of Surgery University of Melbourne  Melbourne VIC 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