Despite a number of prior studies 7–10, the role of MAPT in AD is still unclear. Extending prior work suggesting a significant relationship between the MAPT H1 7 (within the GERAD cohort) and H2 8 (within the ADGC cohort) haplotypes and AD risk, our findings indicate that the A allele of rs393152, which tags the H1 haplotype at the MAPT locus 5, increases risk for AD. Building on prior research demonstrating a robust association between a variant in the H2 haplotype and reduced MAPT brain expression levels 8, we found a dose-dependent effect of the A allele of rs393152 (Figure 3) on intracranial MAPT gene expression. In contrast, we found no association between rs393152 and transcript levels of either synaptophysin or synuclein indicating the specificity of the relationship between the identified AD-PD pleiotropic locus and MAPT transcript expression. Our gene expression findings are consistent with prior work demonstrating a significant relationship between the H1 haplotype and MAPT levels. 32–33 However, a previous study 34 of exon levels from multiple human brain regions found no association between the H1c subhaplotype and
