Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.
Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with epsilon 4.
Li
G
G
Psychiatry Service, Bronx VA Medical Center, NY 10468, USA.
Silverman
J M
JM
Altstiel
L D
LD
Haroutunian
V
V
Perl
D P
DP
Purohit
D
D
Birstein
S
S
Lantz
M
M
Mohs
R C
RC
Davis
K L
KL
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D002423:Cause of Death; D003327:Coronary Disease / Q000235:genetics / Q000401:mortality; D003704:Dementia / Q000235:genetics*; D003710:Demography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D018570:Risk Assessment
D053327:Apolipoprotein E4; D001057:Apolipoproteins E