{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:38:15Z","timestamp":1785209895257,"version":"3.55.0"},"reference-count":99,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>APOE \u025b4 allele confers greatest genetic risk for Alzheimer\u2019s disease (AD), yet mechanisms underlying this risk remain elusive. APOE is involved in lipid metabolism, and literature suggest relationships between high total cholesterol, APOE, and AD. Further investigation is needed to elucidate the potential role of total cholesterol in AD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer\u2019s Disease Neuroimaging Initiative.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Participants ( N\u200a=\u200a1,534) were classified as controls (cognitively normal; N\u200a=\u200a404), early mild cognitive impairment (MCI; N\u200a=\u200a294), late MCI ( N\u200a=\u200a539), or AD ( N\u200a=\u200a297). Total cholesterol levels were compared across APOE genotype and diagnosis. Mendelian randomization was performed to examine causality between total cholesterol and AD risk using APOE as a genetic instrument.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Total cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ ( ps\u200a&lt;\u200a0.04) carriers. Those with AD and late MCI ( ps\u200a&lt;\u200a0.001) had higher total cholesterol than the control group. Comparing APOE4+ to APOE3 carriers, the predicted odds ratios per mg\/dL greater total cholesterol were 1.11 for MCI (95% confidence interval, 1.04\u20137.32), 1.05 for early MCI (1.01\u20133.22), 1.13 for late MCI (1.05\u201311.70), 1.21 for AD (1.09\u201354.05), and 1.13 for composite dementia (MCI or AD; 1.06\u201311.59) ( ps\u200a&lt;\u200a0.05, F-statistics &gt; 10).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Higher total cholesterol may be a significant contributor to AD risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism. Our findings highlight a possible mechanism by which APOE confers AD risk and indicate potential for AD risk modification through maintenance of healthy total cholesterol levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-215091","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T10:28:29Z","timestamp":1640341709000},"page":"1519-1528","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Total Cholesterol and\n                    <i>APOE<\/i>\n                    -Related Risk for Alzheimer\u2019s Disease in the Alzheimer\u2019s Disease Neuroimaging Initiative"],"prefix":"10.1177","volume":"85","author":[{"given":"Michelle M.","family":"Dunk","sequence":"first","affiliation":[{"name":"Department of Psychology, University of Wisconsin \u2013 Milwaukee, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Wisconsin \u2013 Milwaukee, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12328"},{"key":"ref002","unstructured":"KochanekKD, XuJQ, AriasE (2020) Mortality in the United States, 2019, NCHS Data Brief, no 395. 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