{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:47:28Z","timestamp":1787496448801,"version":"build-2736575974"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Background: The APOE \u025b4 allele is the largest genetic risk factor for late-onset Alzheimer\u2019s disease (AD). Recent literature suggested that the contribution of APOE \u025b4 to AD risk could be population-specific, with \u025b4 conferring a lower risk to Blacks or African Americans. Objective: To investigate the effect of APOE haplotypes on AD risk in individuals with European ancestry (EU) and Blacks or African Americans (AA). Methods: We selected data from 1) the National Alzheimer\u2019s Coordinating Center: a total of 3,486 AD cases and 4,511 controls (N\u200a=\u200a7,997, 60% female) with genotypes from the Alzheimer\u2019s Disease Genetics Consortium (ADGC), and 2) the Rush University Religious Orders Study and Memory and Aging Project (ROSMAP) cohort with 578 AD and 670 controls (N\u200a=\u200a1,248, 60% female). Using \u025b3 homozygotes as the reference, we compared the association of various APOE haplotypes with the clinical and neuropathological correlates of dementia in AA and EU. Results: In both cohorts, we find no difference in the odds or age of onset of AD among the \u025b4-linked haplotypes defined by rs769449 within either AA or EU. Additionally, while APOE \u025b4 was associated with a faster rate of decline, no differences were found in rate of decline, clinical or neuropathological features among the \u025b4-linked haplotypes. Further analysis with other variants near the APOE locus failed to identify any effect modification. Conclusion: Our study finds similar effects of the \u025b4-linked haplotypes defined by rs769449 on AD as compared to \u025b3 in both AA and EU. Future studies are required to understand the heterogeneity of APOE conferred risk of AD among various genotypes and populations.<\/jats:p>","DOI":"10.3233\/jad-200228","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T16:02:40Z","timestamp":1601395360000},"page":"467-477","source":"Crossref","is-referenced-by-count":6,"title":["Characterizing Clinical and Neuropathological Traits of APOE Haplotypes in African Americans and Europeans"],"prefix":"10.1177","volume":"78","author":[{"given":"Aziz M.","family":"Mezlini","sequence":"first","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Magdamo","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Merrill","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori B.","family":"Chibnik","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Blacker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Das","sequence":"additional","affiliation":[{"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200228_ref1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jalz.2019.01.010","article-title":"2019 Alzheimer\u2019s disease facts and figures","volume":"15","author":"Alzheimer\u2019s Association","year":"2019","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-200228_ref2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev.genom.1.1.507","article-title":"Apolipoprotein E: Far more than a lipid transport protein","volume":"1","author":"Mahley","year":"2000","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"10.3233\/JAD-200228_ref3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12264-016-0011-3","article-title":"An overview of genome-wide association studies in Alzheimer\u2019s disease","volume":"32","author":"Shen","year":"2016","journal-title":"Neurosci Bull"},{"key":"10.3233\/JAD-200228_ref4","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S1474-4422(16)00127-7","article-title":"Genetic variations underlying Alzheimer\u2019s disease: Evidence from genome-wide association studies and beyond","volume":"15","author":"Cuyvers","year":"2016","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-200228_ref5","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1093\/hmg\/dds491","article-title":"Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer\u2019s disease, multiple sclerosis and endometriosis","volume":"22","author":"Lee","year":"2013","journal-title":"Hum Mol Genet"},{"key":"10.3233\/JAD-200228_ref6","doi-asserted-by":"crossref","first-page":"e79771","DOI":"10.1371\/journal.pone.0079771","article-title":"Alzheimer\u2019s disease: Analyzing the missing heritability","volume":"8","author":"Ridge","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JAD-200228_ref7","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jsbmb.2016.03.012","article-title":"Age, APOE and sex: Triad of risk of Alzheimer\u2019s disease","volume":"160","author":"Riedel","year":"2016","journal-title":"J Steroid Biochem Mol Biol"},{"key":"10.3233\/JAD-200228_ref8","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41582-019-0228-7","article-title":"Apolipoprotein E and Alzheimer disease: Pathobiology and targeting strategies","volume":"15","author":"Yamazaki","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-200228_ref9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1046\/j.1469-1809.1999.6340301.x","article-title":"Apolipoprotein E (APOE) allele distribution in the world. 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