Alzheimer disease risk genes and the age-at-onset phenotype

Despite the recent identification of several novel risk genes for Alzheimer’s disease (AD), little is known about their influence on the age-at-onset (AAO) of AD. The AAO is a phenotype with a heritable component distinct from disease risk and may be a useful trait to study in the context of developing interventions for delaying the onset of AD. We studied the influence of ten recently identified AD risk genes as well as APOE in relation to AAO in a large cohort of AD patients (N=2569). We find that the novel AD risk gene, PICALM exerts a small effect on the AAO of AD with earlier disease onset in risk allele carriers. In addition, we confirmed the previously reported association between the APOE ε4 allele and earlier disease onset. None of the other AD risk genes influenced AAO of AD. Our results suggest that besides APOE, other genes associated with AD risk do not exert large effects on the AAO phenotype of AD.