{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:03:39Z","timestamp":1790229819396,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebral amyloid-beta (A\u03b2) burden does not fully explain variation in Alzheimer\u2019s disease (AD)-related brain structure and episodic memory. We examined whether circulating low-density lipoprotein cholesterol (LDL-C) modifies the cross-sectional statistical association between A\u03b2 burden, the entorhinal cortex (EC) thickness and episodic memory performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cross-sectional data from 1,253 individuals in the Gwangju Alzheimer\u2019s Disease and Related Dementias cohort (798 cognitively normal, 425 mild cognitive impairment, 30 AD dementia) were analyzed. Primary conditional-process models were adjusted for age, sex, education, body mass index, and HbA1c; clinical diagnosis was examined in sensitivity analyses. HC3 heteroskedasticity-consistent inference was used for the focal interaction, and indirect associations were estimated using 10,000 bootstrap resamples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Greater A\u03b2 burden was associated with lower EC thickness (\u03b2 = \u22120.0863,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0012), and EC thickness was positively associated with episodic memory (\u03b2 = 0.3809,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). The unconditional indirect statistical association was supported (\u03b2 = \u22120.0329, 95% bias-corrected bootstrap CI [\u22120.0647, \u22120.0072]). LDL-C modified the A\u03b2\u2013EC association (\u03b2 = \u22120.0937, HC3 SE = 0.0332, 95% CI [\u22120.1589, \u22120.0285],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0049), although the incremental explanatory magnitude was small (\u0394R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.0082). The conditional A\u03b2\u2013EC association was unsupported at approximately 66 mg\/dL LDL-C (\u03b2 = 0.0263,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.583), not statistically supported at approximately 100 mg\/dL (\u03b2 = \u22120.0639,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.060), and negative at 138 mg\/dL (\u03b2 = \u22120.1648,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). The index of moderated indirect association was supported (\u03b2 = \u22120.0357, 95% bias-corrected bootstrap CI [\u22120.0637, \u22120.0119]); conditional indirect associations were most clearly supported at higher LDL-C levels. A similar interaction was observed for non-HDL cholesterol, suggesting that the pattern may reflect a broader atherogenic lipid context.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating LDL-C was associated with modest heterogeneity in the cross-sectional A\u03b2\u2013EC relationship, with more clearly negative conditional associations observed at higher LDL-C levels. Longitudinal studies are needed to determine the temporal and clinical relevance of these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1933036","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:37:50Z","timestamp":1790228270000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Low-density lipoprotein cholesterol modulates amyloid-related entorhinal vulnerability and episodic memory performance in older adults"],"prefix":"10.3389","volume":"18","author":[{"given":"Minh Le","family":"Tran","sequence":"first","affiliation":[{"name":"Division of Digital Health Research, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]},{"name":"Korean Convergence Medical Science, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahye","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Digital Health Research, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeuk U.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Digital Health Research, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]},{"name":"Korean Convergence Medical Science, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Gwangju Alzheimer\u2019s & Related Dementias (GARD) Cohort Research Center, Chosun University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JunHyeong","family":"Do","sequence":"additional","affiliation":[{"name":"Division of Digital Health Research, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]},{"name":"Korean Convergence Medical Science, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Gwangju Alzheimer\u2019s & Related Dementias (GARD) Cohort Research Center, Chosun University","place":["Gwangju, Republic of Korea"]},{"name":"Department of Biomedical Science, Chosun University","place":["Gwangju, Republic of Korea"]},{"name":"Dementia Research Group, Korea Brain Research Institute","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Woo","family":"Seok","sequence":"additional","affiliation":[{"name":"Division of Digital Health Research, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]},{"name":"Korean Convergence Medical Science, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1275932","DOI":"10.3389\/fnins.2023.1275932","article-title":"Lipids and lipoproteins may play a role in the neuropathology of Alzheimer\u2019s disease.","volume":"17","author":"Akyol","year":"2023","journal-title":"Front. 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