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.
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.
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).
The results of this study suggest that education and female gender, not APOE genotype, may be important as independent strong predictive factors for disease progression in patients with EOAD.
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).
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.
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.