Apolipoprotein E Affects Both Myelin Breakdown and Cognition: Implications for Age-Related Trajectories of Decline Into Dementia
Abstract
Background Age-related myelin breakdown is most evident in later-myelinating white matter (LMwm) brain regions. This process might degrade cognitive processing speed (CPS) underlying age-related cognitive decline and the predominance of age as a risk factor for Alzheimer's disease (AD). Apolipoprotein E (ApoE) 4 allele is the second most important AD risk factor. We tested the hypothesis that ApoE4 accelerates age-related slowing in CPS through the process of myelin breakdown. Methods Calculated transverse relaxation rates (R(2)), an indirect magnetic resonance imaging measure of myelin breakdown in LMwm, and measures of CPS were obtained in 22 ApoE4+ and 80 ApoE4-, healthy "younger-old" individuals. To assess specificity, contrasting early-myelinating white matter region and memory task were also examined. Results The CPS versus LMwm R(2) remained significant in the ApoE4+ group even after age was statistically adjusted (r = .65, p = .001) and differed from the correlation observed in the ApoE4- group (Fisher's z test = 3.22, p < .002). No significant associations were observed with the contrast region and memory task in either ApoE subgroup. Conclusions A specific association between CPS and myelin breakdown in LMwm exists in asymptomatic "younger-old" individuals at increased genetic risk for AD. Although inferences of change over time and causality are limited by the cross-sectional study design, this finding lends support to the hypotheses that myelin breakdown underlies age-related slowing in CPS and that by altering the trajectory of myelin breakdown, ApoE alleles shift the age at onset of cognitive decline. Combined use of biomarkers and CPS measures might be useful in developing and targeting primary prevention treatments for AD.
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Myelin loss is accelerated with cognitive impairments.
“such myelin loss is accelerated with cognitive impairments (Bartzokis et al. 2007).”
From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Bartzokis et al. 2007
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- Authors
- Bartzokis, G., Lu, P. H., Geschwind, D. H., Tingus, K., Huang, D., Mendez, M. F., Edwards, N., & Mintz, J.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Bartzokis, George
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 62
- Issue
- 12
- Pages
- 1380-1387
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1964634864
- Cited by
- 109
- References
- 13
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 11
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG027342, P50AG016570)
- National Institute of Mental Health (MH6357-01A1, MH 51928, MH066029-01A2, R01MH066029, R03MH051928)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- apolipoprotein E, APOE ε4, myelin breakdown, processing speed, age-related cognitive decline, Alzheimer's disease risk, transverse relaxation rate, dementia prevention, white matter aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Apolipoproteins E, Cognition Disorders, Dementia, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Sheath, Neuropsychological Tests, Chi-Square Distribution, Genetic Predisposition to Disease
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