While the D14S43 and FOS loci showed no association with either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele was associated with the G allele of the T/G polymorphism located at intron 9 of the PS1 gene (P = 0.016).
We asked the following questions: (1) Does early-onset Alzheimer disease (EOAD) occur in families with predominantly LOAD? and (2) Does the apolipoprotein E (APOE) genotype explain the wide differences in onset age in LOAD families?
These kindreds form the largest collection of AD cases with the same PS-1 mutation and the same educational, environmental, and ethnic background in which to study the phenotypic effect of putative risk factors, such as the epsilon4 allele of apolipoprotein E (ApoE) or head trauma.
Increases in the frequency of allele 1 homozygotes and in the number of non-apolipoprotein E epsilon4 carrying allele 1 homozygotes/heterozygotes was demonstrated in the early-onset AD cases although these values did not reach significance.
The effect of the apolipoprotein E (APOE) epsilon 4 allele on age of onset was analyzed in two groups of families with early-onset Alzheimer's disease (AD), (1) Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2) early-onset non-VG families showing evidence of linkage to chromosome 14.
In late-onset AD, elevated circulating cholesterol levels increase AD risk even after adjusting for the apolipoprotein E ε4 (APOE E4) allele, a major genetic factor for AD and elevated cholesterol levels; however, the role of circulating cholesterol levels in EOAD is unclear.
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.
Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD (<60 years).
presenilin-2 is one of the causative genes for familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor for late-onset and sporadic early-onset Alzheimer's disease.
In this study, we identified 5 (8.3%) LPVs and 18 (30%) VUSs in known dementia-related genes in apolipoprotein E ε4 noncarrying Korean patients with early-onset Alzheimer's disease.
We analyzed the 13 SNPs in the SORL1 gene that had been studied in previous reports using case-control methods and included sex, apolipoprotein E (APOE) genotype, and age at AD onset as covariates.
Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer's disease (EOAD).
Conversely, patients negative for the APOE ɛ4 allele and with early-onset AD are more likely to be predisposed to vulnerability of cerebral networks beyond the medial temporal lobes.