The APOE e4 allele is associated with an earlier onset of amyloid accumulation

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Authors

• Murat Bilgel
• Yang An
• Yun Zhou
• Dean Wong
• Jerry Prince
• Susan Resnick

Abstract

Cerebral amyloid deposition is the defining characteristic of preclinical stages of Alzheimer’s disease (AD) and begins years before cognitive symptoms are evident. The APOE e4 allele is the most influential known genetic risk factor for late-onset AD and is associated with higher cortical amyloid burden in cognitively normal individuals. The presence of one or more e4 alleles shifts the onset of AD to earlier ages. However, the effect of APOE genotype on the age at onset of amyloid accumulation at the individual level has not been investigated. Using data for 132 participants with longitudinal amyloid measures obtained from Pittsburgh compound B (PiB) positron emission tomography scans in the Baltimore Longitudinal Study of Aging, we estimated the age at which each PiB+ individual began accumulating amyloid. We used the Cox model to quantify the risk of accumulating amyloid, and the accelerated failure time model to assess differences in the age at onset of amyloid accumulation in relation to APOE e4 status and sex. APOE e4 positivity conferred a 3-fold risk of accumulating amyloid (chi-squared test p=0.0006) after adjusting for sex and education. On average, e4+ individuals began accumulating amyloid 12.3 years (16.9%, 95% CI 7.4–26.4) earlier than e4- individuals. The average age at onset of amyloid accumulation for the APOE e4- and e4+ groups was 73.1 and 60.7, respectively. Determination of onset age of amyloid accumulation is of critical importance for evaluation of treatments to prevent or delay AD and can inform the optimal time window for anti-amyloid interventions.

Scientific Focus Area: Epidemiology

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