关键词:
qMRI
Quantitative Magnetic Resonance Imaging
APOE
Apolipoprotein E
MWF
Myelin Water Fraction
摘要:
Mounting evidence indicates that myelin breakdown may represent an early phenomenon in neurodegeneration, including Alzheimer's disease (AD). Understanding the factors influencing myelin synthesis and breakdown will be essential for the development and evaluation of therapeutic interventions. In this work, we assessed associations between genetic variance in apolipoprotein E (APOE) and cerebral myelin content. Quantitative magnetic resonance imaging (qMRI) was performed on a cohort of 92 cognitively unimpaired adults ranging in age from 24 to 94 years. We measured whole-brain myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R-1 and R-2 ), sensitive measures of myelin content, in carriers of the APOE epsilon 4 or APOE epsilon 2 alleles and individuals with the epsilon 33 genotype. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between MWF or relaxation rates and APOE isoforms, accounting for confounding variables including age, sex, and race, in several cerebral structures. Our results indicate that carriers of APOE epsilon 2 exhibited significantly higher myelin content, that is, higher MWF, R-1 or R-2 values, in most brain regions investigated as compared to noncarriers, while epsilon 4 carriers exhibited trends toward lower myelin content compared to noncarriers. Finally, all qMRI metrics exhibited quadratic, inverted U-shape, associations with age;attributed to the development of myelination from young to middle age followed by progressive loss of myelin afterwards. Sex and race effects on myelination were, overall, nonsignificant. These findings suggest that individual genetic background may influence cerebral myelin maintenance. Although preliminary, this work lays the foundation for further investigations to clarify the relationship between APOE genotype and myelination, which may suggest potential targets in treatment or prevention of AD