{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:44:37Z","timestamp":1791247477081,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS22\/00071"],"award-info":[{"award-number":["DTS22\/00071"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union","award":["DTS22\/00071"],"award-info":[{"award-number":["DTS22\/00071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The isoform E4 of the Apolipoprotein E (ApoE) represents one of the strongest genetic risk factors for late-onset Alzheimer\u2019s disease (AD). ApoE has key roles in cholesterol transport and amyloid-\u03b2 (A\u03b2) metabolism, which are both central to AD pathogenesis. The E4 isoform has been implicated in reduced cholesterol homeostasis, increased A\u03b2 aggregation, and heightened tau phosphorylation, contributing to amyloid plaques and neurodegeneration. This manuscript examines the complex interactions among ApoE isoforms, cholesterol metabolism, and amyloid pathology. Moreover, the therapeutic challenges associated with lipid-lowering agents (e.g., statins, PCSK9 inhibitors), anti-amyloid immunotherapies, and anticoagulants are described, focusing on ApoE4 carriers. Decision-making challenges are discussed by analyzing the pros and cons of these therapies.<\/jats:p>","DOI":"10.3390\/ijms252212029","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T03:53:14Z","timestamp":1731383594000},"page":"12029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic Challenges Derived from the Interaction Among Apolipoprotein E, Cholesterol, and Amyloid in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-0774","authenticated-orcid":false,"given":"Manuel","family":"Menendez-Gonzalez","sequence":"first","affiliation":[{"name":"Departamento de Medicina, Facultad de Ciencias de la Salud, Universidad de Oviedo, ES-33006 Oviedo, Spain"},{"name":"Servicio de Neurolog\u00eda, Hospital Universitario Central de Asturias, ES-33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), ES-33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a Biological Definition of Alzheimer\u2019s Disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89ra57","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human ApoE Isoforms Differentially Regulate Brain Amyloid-\u03b2 Peptide Clearance","volume":"3","author":"Castellano","year":"2011","journal-title":"Sci. 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