ArticleJournal of Alzheimer's disease : JAD2022
Total Cholesterol and APOE-Related Risk for Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- Betulinaldehyde Ameliorates Aβ-Induced Neurotoxicity and Cognitive Deficits by Modulating the eEF2K/eEF2 Pathway.CNS neuroscience & therapeutics · 2026Article
- Transcriptomic Insights Into Alzheimer's Disease: Differentially Expressed Genes and Cholesterol Metabolism.CNS neuroscience & therapeutics · 2026Article
- Association of a novel nutritional index, the triglyceride-cholesterol-body weight index (TCBI), with incident mild cognitive impairment: CHARLS 2011-2018.Frontiers in nutrition · 2026Article
- Association of genetic predisposition to dyslipidemia and physical activity with incident dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- HMGCR genetic variability in Parkinson's disease in a Spanish cohort: associations with lipid metabolism and early onset.Journal of neurology · 2025Article
- Impact of cardiometabolic conditions on the progression from mild cognitive impairment to dementia: A large cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
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- Impact of diabetes mellitus on the risk of Alzheimer's disease: a mendelian randomization study.BMC neurology · 2024Article
- Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.Neuroscience research · 2024Article
- Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.Brain pathology (Zurich, Switzerland) · 2024Review
- Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.Cellular and molecular neurobiology · 2023Review
- Associations between lipid profiles and late-life cognitive impairment among oldest-old and centenarian adults.MedComm · 2023Article
- Lipid metabolism transcriptomics of murine microglia in Alzheimer's disease and neuroinflammation.Scientific reports · 2023Article
- Machine learning models of Alzheimer's disease spectrum using blood tests.Alzheimer's & dementia (Amsterdam, Netherlands)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAPOEɛ4 allele confers greatest genetic risk for Alzheimer's 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.
objectiveTo investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer's Disease Neuroimaging Initiative.
methodsParticipants (N = 1,534) were classified as controls (cognitively normal; N = 404), early mild cognitive impairment (MCI; N = 294), late MCI (N = 539), or AD (N = 297). 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.
resultsTotal cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ (ps < 0.04) carriers. Those with AD and late MCI (ps < 0.001) 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, 1.04-7.32), 1.05 for early MCI (1.01-3.22), 1.13 for late MCI (1.05-11.70), 1.21 for AD (1.09-54.05), and 1.13 for composite dementia (MCI or AD; 1.06-11.59) (ps < 0.05, F-statistics > 10).
conclusionHigher 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.