Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels.
BACKGROUND
Variation in APOE genotype is a determinant of Alzheimer disease (AD), but the risk associated with variation in plasma apoE levels has yet to be determined. Here, we studied offspring with and without a parental history of AD to identify the effect of plasma apoE levels at middle age on the risk of late-onset AD.


METHODS
Some 203 offspring from 92 families with a parental history of AD were compared with 197 offspring from 97 families without a parental history of AD. APOE genotypes and plasma apoE levels were assessed in all offspring. Difference in plasma apoE level between subjects with and without a parental history of AD was calculated using robust linear regression, both stratified and adjusted for APOE genotype.


RESULTS
Offspring with a parental history of AD were more likely to be an APOE epsilon4 allele carrier (46% vs 21%, p < 0.001) than offspring without such a parental history. Mean plasma apoE levels strongly decreased from epsilon2 to epsilon3epsilon3 to epsilon4 carriers (p < 0.001). Offspring with a parental history of AD had lower plasma apoE levels than subjects without such a history, both in analyses adjusted for APOE genotype (difference: -0.21 mg/dL, p = 0.02) and when using standardized Z scores, when stratified for APOE genotype (difference: -0.22, p = 0.009).


CONCLUSIONS
Our findings suggest that lower plasma apoE levels in middle age could be a risk factor for Alzheimer disease in old age, independent of APOE genotype.
van Vliet
P
P
Leiden University Medical Center, Department of Gerontology and Geriatrics (C2-R), PO Box 9600, 2300 RC, Leiden, The Netherlands. p.van_vliet@lumc.nl
Westendorp
R G J
RG
Eikelenboom
P
P
Comijs
H C
HC
Frölich
M
M
Bakker
E
E
van der Flier
W
W
van Exel
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000032:analysis / Q000097:blood* / Q000235:genetics*; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010290:Parents; D010375:Pedigree; D011446:Prospective Studies
D001057:Apolipoproteins E