Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes.
Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
Among patients and control subjects similar in age, gender, and ethnic group from the New York City community of Washington Heights-Inwood, we found that the odds ratio (OR) for AD associated with homozygosity for APO-epsilon 4 was 17.9 (95% confidence interval [CI], 4.6-69.8) and that associated with heterozygosity for APO-epsilon 4 was 4.2 (95% CI, 1.8-9.5) compared with persons with other APO-E genotypes.
We examined the possibility that commonly observed variability in A beta deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with A beta in vitro.
By contrast with the beta APP mutants, no particular allele of the apolipoprotein E (APOE) gene predicts the disease completely but one allele is associated with the disease suggesting APOE is a risk locus for AD.
The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014).
Are the associations between Alzheimer's disease and polymorphisms in the apolipoprotein E and the apolipoprotein CII genes due to linkage disequilibrium?
There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.
These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.
Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD).
Analyses of beta PP missense mutations and of the effects of apolipoprotein E genotype lend new support to the hypothesis that accelerated amyloid beta protein deposition plays a pivotal role in the genesis of Alzheimer's disease.
To clarify the association of ApoE polymorphism with Alzheimer's disease and vascular dementia in Japan, 13 patients with early onset (age > or = 65) sporadic Alzheimer's disease, 40 patients with late onset (age < or = 65) sporadic Alzheimer's disease, 19 patients with vascular dementia, and 49 non-demented control subjects were analysed.
Our independent finding of a marked association of ApoE epsilon 4 allele with AD further supports a possible role of ApoE in the pathogenesis of AD and confirms the study of Saunders et al (Neurology 1993;43:1467-1472).