APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds
Donald M Lyall1,2,3,4, Susana Muñoz Maniega1,2,5, Sarah E Harris1,4
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Background:
Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease.
Aim And/Or Hypothesis:
To test for independent associations between two Alzheimer's disease-susceptibility gene loci--APOE ε and the TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults.
Methods:
Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71-74).
Results:
No significant effects of APOE ε or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants.
Conclusions:
Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature.
Insights
This study found no link between Alzheimer's disease (AD) gene variants APOE ε and TOMM40 and markers of small vessel disease in older adults. Further research is needed to understand these complex relationships.
Area of Science:
- Neuroscience
- Genetics
- Gerontology
Background:
- Cerebral small vessel disease (CSVD) markers like white matter hyperintensities and cerebral microbleeds are common in Alzheimer's disease (AD).
- Investigating genetic factors associated with AD susceptibility is crucial for understanding disease mechanisms.
Purpose of the Study:
- To examine the independent associations of two AD-susceptibility gene loci, APOE ε and TOMM40 '523' poly-T repeat, with CSVD markers.
- To assess white matter hyperintensities and cerebral microbleed burden in community-dwelling older adults.
Main Methods:
- Genotyping for APOE ε and TOMM40 '523' was performed on 624 participants from the Lothian Birth Cohort 1936.
- Detailed structural brain magnetic resonance imaging was conducted at a mean age of 72.7 years.
Main Results:
- No significant associations were found between APOE ε or TOMM40 '523' genotypes and white matter hyperintensities.
- Similarly, no significant effects were observed for cerebral microbleed burden in relation to these gene loci.
Conclusions:
- The lack of association suggests that these specific AD susceptibility genes may not directly influence CSVD markers in this relatively healthy cohort.
- Findings may indicate that the health status of the studied population influences the observed genetic associations compared to other studies.
Related Concept Videos
01:17Hemorrhagic Stroke l: Introduction
01:29Alzheimer Disease l: Introduction