Apolipoprotein E genotype is related to progression of white matter lesion load.
OBJECTIVE
The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment.


METHODS
The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression.


RESULTS
Multivariable analyses showed that epsilon4epsilon4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon4 allele for apolipoprotein E genotype.


CONCLUSIONS
These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia.
Godin
Ophélia
O
Inserm Unit 708 Neuroepidemiology, Hôpital la Salpétrière, Paris, France. ophelia.godin@upmc.fr
Tzourio
Christophe
C
Maillard
Pauline
P
Alpérovitch
Annick
A
Mazoyer
Bernard
B
Dufouil
Carole
C
D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics; D012720:Severity of Illness Index
D053327:Apolipoprotein E4; D001057:Apolipoproteins E