Next to APOE-ɛ4 homozygosity, we found that all four affected family members carried a rare variant in the VPS10 domain of the SORL1 gene, associated with AβPP processing and AD risk.
Numerous studies have tested for associations between common variants of the angiotensin-converting enzyme gene (ACE) and late-onset Alzheimer disease (AD), but results have been inconclusive.
In addition, a logistic regression analysis also conferred positive association between the SNP rs760678 and LOAD (dominant model: OR=2.10, 95% CI=1.23-3.58, P=0.007; additive model: OR=1.37, 95% CI=1.09-1.74, P=0.008) after adjustment for age, gender, and the APOE ε4 carrier status.
Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s.
These results indicate that differences in brain activity are evident in cognitively intact individuals who are at risk for late-onset Alzheimer's disease by virtue of their APOE allele status.
In this study, we report that common single nucleotide polymorphism (SNP) variation in BACE2 is associated with altered AD risk in apolipoprotein E gene (APOE) epsilon 4 variant (ε4) non-carriers.
We also assessed whether AD-related variants and APOE alleles were associated with CIND status, either individually or as part of a composite genetic risk score.
This study provides empirical support for the suggestion that the APOE locus is the major susceptibility gene for late-onset AD in the human genome, with an OR significantly greater than any other locus in the human genome.
The bridging integrator 1 (BIN1) gene, also known as amphiphysin 2, has recently been identified as the most important risk locus for late onset Alzheimer's disease (LOAD), after apolipoprotein E (APOE).
These findings may help define the mechanisms that APOE4 contribute that increase risk for AD and identify new candidate genes conferring susceptibility to AD.
Phenotypes of apolipoprotein E (apo E) were determined by the iso-electric focusing method in 42 Japanese patients with nonfamilial late-onset Alzheimer's disease (AD) and 96 age-matched controls without hyperlipidemia and/or diabetes.
In conclusion, this haplotype-phenotype analysis of apoE expression in PMB suggests that either; (1) the cis-regulation of APOE expression levels extends far upstream of the APOE promoter or (2) an APOE epsilon4 allele independent mechanism involving the TOMM40 gene plays a role in the risk of AD.
We show here that such an analysis can miss strong genetic association signals, such as that of the apolipoprotein-e gene in late-onset Alzheimer disease.
We suggest that this long transcript may alter the normal pathway for processing of amyloid precursor protein, the protein which appears to be central in the pathogenesis of AD.
Although we did not replicate the earlier association between the APOE 3-TOMM40 haplotypes and age at onset, we observed that the polyT polymorphism is associated with risk of LOAD in APOE 33 homozygotes in a large case-control series but in the opposite direction as in the previous study.