{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:11:56Z","timestamp":1783944716690,"version":"3.55.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of defense ADNI","award":["W81XWH-12-2-0012"],"award-info":[{"award-number":["W81XWH-12-2-0012"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is the most common form of dementia, marked by progressive cognitive decline. Low-density lipoprotein cholesterol (LDL-C) has been implicated in AD pathology, but findings remain inconsistent. Apolipoprotein E4 (APOE4) status and sex may contribute to this variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine how LDL-C association with neurodegeneration in AD patients, differ according to APOE4 status and gender.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We stratified 106 AD patients by APOE4 status and sex into four subgroups: male APOE4+, female APOE4+, male APOE4\u2212, and female APOE4\u2212. Longitudinal cortical thickness changes were assessed using magnetic resonance imaging (MRI). We examined the association between LDL-C levels and cortical thinning within each subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In APOE4-positive females, higher LDL-C levels were significantly associated with accelerated cortical thinning in several regions, including the parahippocampal (\u03b2\u2009=\u2009\u22120.0075, p\u2009=\u20090.017), medial orbitofrontal (\u03b2\u2009=\u2009\u22120.0025, p\u2009=\u20090.028), fusiform (\u03b2\u2009=\u2009\u22120.0047, p\u2009=\u20090.034), posterior cingulate (\u03b2\u2009=\u2009\u22120.0097, p\u2009=\u20090.006), and inferior temporal cortices (\u03b2\u2009=\u2009\u22120.0085, p\u2009=\u20090.019). This subgroup also showed a significant association between LDL-C and MMSE decline (\u03b2\u2009=\u2009\u22121.409, p\u2009=\u20090.014) as well as longitudinal increases in cerebrospinal fluid phosphorylated tau181 (\u03b2\u2009=\u20090.014, p\u2009=\u20090.039). These effects were not observed in other subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated LDL-C is associated with increased neurodegeneration and cognitive decline in female AD patients carrying the APOE4 allele. These exploratory findings highlight a subgroup-specific vulnerability to lipid-related neurodegeneration in AD and underscore the importance of considering both sex and genetic background in future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261422449","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T14:40:24Z","timestamp":1773412824000},"page":"1214-1224","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased vulnerability to low-density lipoprotein cholesterol in apolipoprotein E4-positive females: Longitudinal effects on neurodegeneration and cognition"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4431-7682","authenticated-orcid":false,"given":"Abdul Jaber","family":"Tayem","sequence":"first","affiliation":[{"name":"University of Jordan, School of Medicine"},{"name":"Cedars-Sinai Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-6954","authenticated-orcid":false,"given":"Ahmad Bani","family":"Jaber","sequence":"additional","affiliation":[{"name":"University of Jordan, Department of Pharmaceutics and Pharmaceutical Technology, Amman, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-223X","authenticated-orcid":false,"given":"Ahmad M.","family":"Altantawi","sequence":"additional","affiliation":[{"name":"University of Jordan, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3505-4842","authenticated-orcid":false,"given":"Noor M.","family":"Masadeh","sequence":"additional","affiliation":[{"name":"University of Jordan, School of Medicine"},{"name":"Istiklal Hospital, Amman, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6298-9646","authenticated-orcid":false,"given":"Laith","family":"Al Quran","sequence":"additional","affiliation":[{"name":"University of Jordan, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3359-1204","authenticated-orcid":false,"given":"Omar","family":"Al-Jammal","sequence":"additional","affiliation":[{"name":"University of Jordan, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative *","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.01.016"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-021-02449-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01886-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.05.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00574-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(21)00150-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215091"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2025.105825"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-013-0468-2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00044"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000194507.39504.17"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.727289"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000161870.78572.A5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.5.705"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117324"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.844066"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1161527"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-013-9272-x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24135"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15657"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01642-5"},{"key":"e_1_3_3_24_2","article-title":"APOE \u03954\u2013associated heterogeneity of neuroimaging biomarkers across the Alzheimer\u2019s disease continuum","volume":"21","author":"Mares J","year":"2024","unstructured":"Mares J, Kumar G, Sharma A, et al. 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