Correlations between apolipoprotein E epsilon4 gene dose and whole brain atrophy rates.
OBJECTIVE
The purpose of this study was to characterize the relationship between whole brain atrophy rates and three levels of genetic risk for Alzheimer's disease in cognitively normal persons. The authors previously found accelerated whole brain atrophy rates in patients with probable Alzheimer's disease by computing changes in brain volume from sequential magnetic resonance images (MRIs).


METHODS
The authors assessed 36 late-middle-aged persons from three genetic groups: those with two, one, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's disease susceptibility gene. The participants had clinical ratings, neuropsychological tests, and volumetric T1-weighted MRIs during a baseline visit and again approximately 2 years later. Two different image-analysis techniques, brain boundary shift integration and iterative principal component analysis, were used to compute whole brain atrophy rates.


RESULTS
While there were no baseline, follow-up, or between-visit differences in the clinical ratings or neuropsychological test scores among the three subject groups, whole brain atrophy rates were significantly greater in the epsilon4 homozygote group than in noncarriers and were significantly correlated with epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype).


CONCLUSIONS
Since APOE epsilon4 gene dose is associated with an increased risk of Alzheimer's disease and a younger median age at dementia onset, this study suggests an association between the risk of Alzheimer's disease and accelerated brain atrophy rates before the onset of cognitive impairment.
Chen
Kewei
K
Banner Alzheimer Institute, Banner Good Samaritan PET Center, 1111 E. McDowell Rd., Phoenix, AZ 85006, USA. kchen@math.la.asu.edu
Reiman
Eric M
EM
Alexander
Gene E
GE
Caselli
Richard J
RJ
Gerkin
Richard
R
Bandy
Daniel
D
Domb
Alisa
A
Osborne
David
D
Fox
Nick
N
Crum
William R
WR
Saunders
Ann M
AM
Hardy
John
J
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D012307:Risk Factors; D013997:Time Factors
D053327:Apolipoprotein E4