In our previous studies using this approach we have successfully validated hypothesized effects of rs2986019 in CALHM1 on CSF Aβ42 levels [19], generated testable biological hypotheses for AD implicated variants [16], and identified novel variants in MAPT and PPP3R1 that are associated with both biomarker levels and rate of progression of AD [14], [17]. This evidence concerns the gene MAPT and Alzheimer disease.