ArticleNeuroImage. Clinical2019
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects.
Article in NeuroImage. Clinical, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- DTI-ALPS Primarily Reflects White Matter Diffusion Dispersion and Microstructural Heterogeneity in Neurodegeneration: Insights From Multi-Modal MRI.Human brain mapping · 2026Article
- Integrated imaging and molecular profiling reveals APOE4-associated neurovascular and glial disruptions in young adult mice.Journal of neuroinflammation · 2026Article
- T1-weighted/T2-weighted ratio reflects microstructural changes in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- History of Traumatic Brain Injury with Loss of Consciousness and APOEbioRxiv : the preprint server for biology · 2026Article
- Association of the methylation of age-related epigenetic marker ELOVL2 with neurophysiological alterations and immunosenescence during aging and its modulation by the APOE genotype.Frontiers in immunology · 2026Article
- Glymphatic and meningeal lymphatic dysfunction in Alzheimer's disease: Mechanisms and therapeutic perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Alzheimer's Disease-Like Brain Pattern Biomarker: Capturing Risks and Predicting Disease Onset.Research square · 2025Article
- Development and Validation of a Tool to Predict Onset of Mild Cognitive Impairment and Alzheimer Dementia.JAMA network open · 2025Article
- Elevated blood glucose levels are associated with the progression of brain hypometabolism, and HDL-C andmedRxiv : the preprint server for health sciences · 2024Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- A comprehensive analysis of APOE genotype effects on human brain structure in the UK Biobank.Translational psychiatry · 2024Article
- Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.European journal of nuclear medicine and molecular imaging · 2024Article
- Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Prognostic Value of Gut Microbiome for Conversion from Mild Cognitive Impairment to Alzheimer's Disease Dementia within 4 Years: Results from the AlzBiom Study.International journal of molecular sciences · 2024Article
- The interaction effects of age, APOE and common environmental risk factors on human brain structure.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status.Alzheimer's research & therapy · 2024Article
- Article
- APOE4-promoted gliosis and degeneration in tauopathy are ameliorated by pharmacological inhibition of HMGB1 release.Cell reports · 2023Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the myelin sheath along axons, rather than pure axonal degeneration. Considering the main role of APOE in brain lipid transport, characterizing the impact of APOE on the myelin coating is therefore of crucial interest, especially in healthy APOE-ε4 homozygous individuals, who are exposed to a twelve-fold higher risk of developing Alzheimer's disease (AD), compared to the rest of the population. We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content. Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles. These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade.
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