{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:08:48Z","timestamp":1789236528897,"version":"build-2803163510"},"reference-count":127,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM133440"],"award-info":[{"award-number":["R35GM133440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21AG096297"],"award-info":[{"award-number":["R21AG096297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder where age, genetic factors and sleep disturbance significantly influence disease risk. Recent genome-wide association studies identified a C\/T missense variant (rs141749679) in the sortilin (SORT1) gene linked to heightened AD risk, revealing SORT1\u2019s role as a key player in the disease\u2019s pathophysiology. This type I membrane glycoprotein is implicated in amyloid \u03b2 (A\u03b2) accumulation and associated lipid dysregulation, particularly through its interaction with apolipoprotein E (ApoE). SORT1 facilitates the uptake of ApoE-bound polyunsaturated fatty acids (PUFAs), conversion to endocannabinoids (eCBs), and the regulation of anti-inflammatory pathways via peroxisome proliferator-activated receptors (PPARs). Notably, this neuroprotective signaling is contingent on the APOE allele, exhibiting functionality in presence of ApoE3 but disrupted with ApoE4. Additionally, the brain-type fatty acid binding protein, FABP7, mediates this signaling cascade, emphasizing its role in neuron-glia communication. FABP7 is known to regulate sleep across species and binds PUFAs and eCBs. Therefore, dysfunction of the ApoE-SORT1-FABP7 axis may underlie the neuroprotective loss observed in AD, linking sleep disruption and lipid homeostasis to disease progression. This perspective aims to elucidate the intricate neural-glial mechanisms governing the ApoE-SORT1-FABP7 interaction and their implications for targeting therapeutic interventions in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/biom15101432","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T09:45:01Z","timestamp":1760089501000},"page":"1432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer\u2019s Disease Pathophysiology"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-0906","authenticated-orcid":false,"given":"Carlos C.","family":"Flores","sequence":"first","affiliation":[{"name":"Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-3342","authenticated-orcid":false,"given":"Yool","family":"Lee","sequence":"additional","affiliation":[{"name":"Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA"},{"name":"Sleep and Performance Research Center, Washington State University, Spokane, WA 99202, USA"},{"name":"Steve Gleason Institute for Neuroscience, Washington State University, Spokane, WA 99202, USA"},{"name":"Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Spokane, WA 99202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-928X","authenticated-orcid":false,"given":"Christopher J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA"},{"name":"Sleep and Performance Research Center, Washington State University, Spokane, WA 99202, USA"},{"name":"Steve Gleason Institute for Neuroscience, Washington State University, Spokane, WA 99202, USA"},{"name":"Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Spokane, WA 99202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-9844","authenticated-orcid":false,"given":"Patrick","family":"Solverson","sequence":"additional","affiliation":[{"name":"Nutrition and Exercise Physiology, Elson S. 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Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA"},{"name":"Sleep and Performance Research Center, Washington State University, Spokane, WA 99202, USA"},{"name":"Steve Gleason Institute for Neuroscience, Washington State University, Spokane, WA 99202, USA"},{"name":"Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Spokane, WA 99202, USA"},{"name":"College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA"},{"name":"Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1534","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic burden of Alzheimer\u2019s disease and other dementias: Estimates and projections for 152 countries or territories","volume":"12","author":"Chen","year":"2024","journal-title":"Lancet Glob. 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