{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:06:35Z","timestamp":1792796795916,"version":"4.5.0"},"reference-count":182,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T00:00:00Z","timestamp":1545782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARF-16-443213"],"award-info":[{"award-number":["AARF-16-443213"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["ES024233"],"award-info":[{"award-number":["ES024233"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG056371"],"award-info":[{"award-number":["AG056371"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG057565"],"award-info":[{"award-number":["AG057565"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["K01AG044490"],"award-info":[{"award-number":["K01AG044490"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-13-1-0384"],"award-info":[{"award-number":["W81XWH-13-1-0384"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia worldwide. The extracellular deposits of Amyloid beta (A\u03b2) in the brain\u2014called amyloid plaques, and neurofibrillary tangles\u2014intracellular tau aggregates, are morphological hallmarks of the disease. The risk for AD is a complicated interplay between aging, genetic risk factors, and environmental influences. One of the Apolipoprotein E (APOE) alleles\u2014APOE\u03b54, is the major genetic risk factor for late-onset AD (LOAD). APOE is the primary cholesterol carrier in the brain, and plays an essential role in lipid trafficking, cholesterol homeostasis, and synaptic stability. Recent genome-wide association studies (GWAS) have identified other candidate LOAD risk loci, as well. One of those is the triggering receptor expressed on myeloid cells 2 (TREM2), which, in the brain, is expressed primarily by microglia. While the function of TREM2 is not fully understood, it promotes microglia survival, proliferation, and phagocytosis, making it important for cell viability and normal immune functions in the brain. Emerging evidence from protein binding assays suggests that APOE binds to TREM2 and APOE-containing lipoproteins in the brain as well as periphery, and are putative ligands for TREM2, thus raising the possibility of an APOE-TREM2 interaction modulating different aspects of AD pathology, potentially in an isoform-specific manner. This review is focusing on the interplay between APOE isoforms and TREM2 in association with AD pathology.<\/jats:p>","DOI":"10.3390\/ijms20010081","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T11:31:21Z","timestamp":1545823881000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["The Role of APOE and TREM2 in Alzheimer\u2032s Disease\u2014Current Understanding and Perspectives"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-4944","authenticated-orcid":false,"given":"Cody M.","family":"Wolfe","sequence":"first","affiliation":[{"name":"Department of Environmental &amp; Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F.","family":"Fitz","sequence":"additional","affiliation":[{"name":"Department of Environmental &amp; Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong Nyon","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Environmental &amp; Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliya","family":"Lefterov","sequence":"additional","affiliation":[{"name":"Department of Environmental &amp; Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radosveta","family":"Koldamova","sequence":"additional","affiliation":[{"name":"Department of Environmental &amp; Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-017-0297-z","article-title":"Alzheimer\u2019s disease prevention: From risk factors to early intervention","volume":"9","author":"Minguillon","year":"2017","journal-title":"Alzheimers Res. 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