{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:10:47Z","timestamp":1779149447924,"version":"3.51.4"},"reference-count":81,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour la Recherche sur la Maladie d\u2019Alzheimer SAO-FRA","award":["2017\/002"],"award-info":[{"award-number":["2017\/002"]}]},{"name":"Fondation M\u00e9dicale Reine Elisabeth FMRE-GSKE","award":["\u20ac 180.000,2020-2022"],"award-info":[{"award-number":["\u20ac 180.000,2020-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,23]]},"abstract":"<jats:p>\n                    Among genetic susceptibility loci associated with late-onset Alzheimer disease (LOAD), genetic polymorphisms identified in genes encoding lipid carriers led to the hypothesis that a disruption of lipid metabolism could promote disease progression. We previously reported that amyloid precursor protein (APP) involved in Alzheimer disease (AD) physiopathology impairs lipid synthesis needed for cortical networks\u2019 activity and that activation of peroxisome proliferator\u2013activated receptor \u03b1 (PPAR\u03b1), a metabolic regulator involved in lipid metabolism, improves synaptic plasticity in an AD mouse model. These observations led us to investigate a possible correlation between PPAR\u03b1 function and full-length APP expression. Here, we report that PPAR\u03b1 expression and activation were inversely related to APP expression both in LOAD brains and in early-onset AD cases with a duplication of the\n                    <jats:italic>APP<\/jats:italic>\n                    gene, but not in control human brains. Moreover, human APP expression decreased\n                    <jats:italic>PPARA<\/jats:italic>\n                    expression and its related target genes in transgenic mice and in cultured cortical cells, while opposite results were observed in APP-silenced cortical networks. In cultured neurons, APP-mediated decrease or increase in synaptic activity was corrected by a PPAR\u03b1-specific agonist and antagonist, respectively. APP-mediated control of synaptic activity was abolished following PPAR\u03b1 deficiency, indicating a key function of PPAR\u03b1 in this process.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.150099","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T12:00:45Z","timestamp":1625572845000},"source":"Crossref","is-referenced-by-count":21,"title":["Regulation of PPAR\u03b1 by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6745-3811","authenticated-orcid":true,"given":"Francisco","family":"S\u00e1ez-Orellana","sequence":"first","affiliation":[{"name":"Alzheimer Dementia Group and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Leroy","sequence":"additional","affiliation":[{"name":"Alzheimer Dementia Group 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