{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T17:01:38Z","timestamp":1794243698079,"version":"4.9.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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>Background<\/jats:title>\n                    <jats:p>Growing evidence suggests that both ApoE genotype and metabolic disturbances including insulin resistance (IR) and obesity constitute risk factors for Alzheimer\u2019s disease (AD). However, large-scale studies investigating whether ApoE genotype interacts with metabolic abnormalities to indirectly impair cognitive function in AD remain scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This cross-sectional study aimed to explore the associations between ApoE genotype, metabolic disturbances [IR assessed by triglyceride-glucose (TyG) index and body mass index (BMI)], and cognitive function in AD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 1,162 clinically diagnosed probable AD patients from the Cognitive Impairment Clinic at Tianjin Huanhu Hospital. Participants were categorized by ApoE \u03b54 carrier status. Metabolic parameters were evaluated using the TyG index and BMI. Mediation effect models were employed to assess the relationships between ApoE genotype, metabolic indices, and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ApoE \u03b54 carriers exhibited significantly lower BMI (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001) and higher TyG index (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001) compared to non-ApoE \u03b54 carriers. Significant TyG index elevation in ApoE \u03b54 carriers was observed in AD patients with Mini-Mental State Examination (MMSE) &amp;gt; 20 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0036) and MMSE 10\u201320 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.009). Mediation analysis revealed that ApoE \u03b54 exerted 73.4% of its negative effect on cognition through direct pathways, while 9.7 and 16.9% were mediated through BMI reduction and TyG elevation, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ApoE \u03b54 carriers demonstrate a distinct metabolic profile characterized by lower BMI and elevated TyG index, associated with poorer cognitive performance. Our findings suggest that ApoE \u03b54 may indirectly influence AD cognition through metabolic pathways, highlighting early interventions targeting ApoE-related metabolic dysregulation as potential strategies to delay AD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1731547","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:54:29Z","timestamp":1771397669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Insulin resistance (TyG index) and body mass index as metabolic biomarker combined with ApoE genotype to diagnose Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Renyu","family":"Chen","sequence":"first","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]},{"name":"Anqiu City People\u2019s Hospital","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Fan","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cihan","family":"Di","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]},{"name":"The Second Affiliated Hospital of Qiqihar Medical College","place":["Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Shi","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Lv","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ji","sequence":"additional","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Huanhu Hospital, Tianjin Dementia Institute","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100498","DOI":"10.1016\/j.jlr.2024.100498","article-title":"APOE genotype dictates lipidomic signatures in primary human hepatocytes.","volume":"65","author":"Almeida","year":"2024","journal-title":"J. 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