You’ve heard of Alzheimer’s disease, but did you know that APOE4 homozygosity represents a distinct genetic form of this condition? A recent study published in Nature Medicine sheds light on the impact of APOE4 homozygosity on Alzheimer’s disease, revealing it as a unique genetic factor.
The study, led by Juan Fortea and Víctor Montal, analyzed data from the National Alzheimer’s Coordinating Center and five large cohorts with AD biomarkers. The research included 3,297 individuals for the pathological study and 10,039 for the clinical study.
Findings from the study showed that almost all individuals with APOE4 homozygosity exhibited Alzheimer’s disease pathology and had significantly higher levels of AD biomarkers starting from age 55 compared to those with APOE3 homozygosity. By age 65, nearly all APOE4 homozygotes had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, indicating near-full penetrance of AD biology in this group.
Interestingly, the age of symptom onset was earlier in APOE4 homozygotes at 65.1, with a more narrow prediction interval than APOE3 homozygotes. The predictability of symptom onset and the sequence of biomarker changes in APOE4 homozygotes resembled those seen in autosomal dominant AD and Down syndrome.
However, in the dementia stage, there were no differences in amyloid or tau positron emission tomography across haplotypes, despite earlier clinical and biomarker changes. The study concluded that APOE4 homozygotes represent a genetic form of AD, suggesting the need for individualized prevention strategies, clinical trials, and treatments.
Overall, this study provides valuable insights into the role of APOE4 homozygosity in Alzheimer’s disease, highlighting it as a distinct genetic factor that influences the clinical, pathological, and biomarker characteristics of the condition.