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 MAPT expression indicating that additional work using large samples is needed to systematically investigate the H1/H2 sub-haplotypes and MAPT brain expression levels. Additionally, building on prior work detecting smaller gray matter volumes within cognitively normal 35 and cognitively impaired 36 MAPT carriers, we found a significant relationship between the A allele of rs393152 and longitudinal atrophy of the entorhinal cortex and hippocampus, two medial temporal lobe regions selectively affected with tau-associated neurofibrillary pathology in the earliest stages of AD. Considered together, this suggests that the PD-associated MAPT cluster influences Alzheimer’s neurodegeneration likely via tau-related mechanisms.
