{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:02:10Z","timestamp":1788912130109,"version":"build-2803163510"},"reference-count":273,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82271446"],"award-info":[{"award-number":["82271446"]}]},{"name":"National Natural Science Foundation of China","award":["82471442"],"award-info":[{"award-number":["82471442"]}]},{"name":"National Natural Science Foundation of China","award":["2024BCA003"],"award-info":[{"award-number":["2024BCA003"]}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["82271446"],"award-info":[{"award-number":["82271446"]}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["82471442"],"award-info":[{"award-number":["82471442"]}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["2024BCA003"],"award-info":[{"award-number":["2024BCA003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Lipid metabolism disorders represent a significant risk factor for the pathogenesis of Alzheimer\u2019s disease (AD). Apolipoprotein E (APOE) has been regarded as a pivotal regulator of lipid homeostasis in the central nervous system (CNS), with polymorphic alleles identified as genetic risk factors for late-onset AD. Despite advances in APOE research and the development of numerous pharmaceutical approaches targeting distinct APOE isoforms, there remain limited treatment approaches for AD that focus on lipid metabolic homeostasis. Consequently, it is necessary to reevaluate the lipid metabolic process in the CNS. Apolipoprotein A1 (APOA-I), a major component of high-density lipoprotein (HDL), plays a crucial role in reverse cholesterol transport from tissues to the liver to maintain lipid homeostasis. Over the past few decades, numerous studies have suggested a connection between reduced APOA-I levels and a higher risk of AD. APOA-I is synthesized exclusively in the liver and intestines, and there is a lack of conclusive evidence supporting its functional significance within the central nervous system, in contrast to APOE, which is produced locally by glial cells and neurons within the CNS. Moreover, APOA-I\u2019s ability to penetrate the blood-brain barrier (BBB) is still poorly understood, which causes its significance in central lipid metabolism and AD pathophysiology to be mainly disregarded. Recent advancements in tracing methodologies have underscored the essential role of APOA-I in regulating lipid metabolism in the CNS. This review aims to elucidate the physiological functions and metabolic pathways of APOA-I, integrating its associations with AD-related pathologies, risk factors, and potential therapeutic targets. Through this discourse, we aim to provide novel insights into the intricate relationship between AD and APOA-I, paving the way for future research in this field.<\/jats:p>","DOI":"10.3390\/ph18060790","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:39:36Z","timestamp":1748205576000},"page":"790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Role of APOA-I in Alzheimer\u2019s Disease: Bridging Peripheral Tissues and the Central Nervous System"],"prefix":"10.3390","volume":"18","author":[{"given":"Guanfeng","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6616-3154","authenticated-orcid":false,"given":"Yuwei","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingwan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-5972","authenticated-orcid":false,"given":"Jing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2024). 2024 Alzheimer\u2019s disease facts and figures. 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