Those candidate genes include apolipoprotein E (APOE), catechol-O-methyltransferase (COMT) (Komulainen et al., 2008), brain-derived neurotrophic factor (BDNF) (Bray et al., 2005), and dystrobrevin-binding protein 1 (DTNBP1) (Wray et al., 2008), with the APOE ε4 allele being by far the strongest genetic risk factor and accounts for about 5% of the variance in lifetime cognitive change and 4% of the variance in AD. Here, COMT is linked to Alzheimer disease.