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[P‐063]: The impact of ApoE alleles on age‐related myelin breakdown
Author(s) -
Bartzokis George,
Lu Po H.,
Geschwind Daniel H.,
Edwards Nancy,
Mintz Jim,
Cummings Jeffrey L.
Publication year - 2005
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2005.06.137
Subject(s) - apolipoprotein e , myelin , allele , corpus callosum , white matter , biology , neuroscience , age of onset , medicine , genetics , central nervous system , disease , magnetic resonance imaging , gene , radiology
Background: By shifting the age at onset of Alzheimer’s disease (AD), Apolipoprotein E (ApoE) genotype is the most influential AD risk factor after age itself. ApoE4 alleles decrease while ApoE2 alleles increase age at onset. Human and non-human primate data suggest that in middle age, the structural integrity of myelin sheaths begins breaking down with an accelerating age-related trajectory most evident in the brain’s later-myelinating association regions. This results in a progressive “disconnection” of widely distributed neural networks that may underlie the age risk factor for AD. Objective: Assess whether ApoE genotype shifts the age at onset of AD by altering the trajectory of age-related myelin breakdown.Methods: Healthy individuals (N 104) between 55 and 75 years of age were ApoE genotyped. The late-myelinating frontal lobe white matter (Fwm) as well as earlyand later-myelinating regions of the corpus callosum, the splenium (Swm) and genu (Gwm) respectively, were assessed using MRI and transverse relaxation rates (R2) were calculated. R2 is an indirect measure of white matter structural integrity; it declines with age-related myelin breakdown and is significantly lower in AD. As hypothesized, presence of the protective ApoE2 allele was associated with significantly higher R2 values in Fwm and Gwm, but not in Swm. Furthermore, ApoE status impacted the trajectory of age-related myelin breakdown in late-myelinating regions (Fwm and Gwm) but not in the Swm. In the Fwm and Gwm ApoE4 individuals had a steeper slope of decline in R2 with age than ApoE2 individuals, while Apoe3 individuals had an intermediate slope. Conclusions: These data suggest that the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. The findings are consistent with the hypothesis that later-myelinating regions are more susceptible to the myelin breakdown process and that this process may determine the age at onset of AD. Combining ApoE status with non-invasive measures of myelin breakdown may be useful in designing treatment studies directed at primary prevention of AD.