From an AD perspective, these results highlight the importance of considering tau. Recent evidence indicates that dominantly inherited mutations in MAPT cause forms of frontotemporal dementia with parkinsonism 29, a rare MAPT variant (p.A152T) increases risk for AD and frontotemporal dementia syndromes 37 and tau modulates Aβ-associated Alzheimer’s neurodegeneration. 38 Consistent with this work, our present results indicate that tau-associated polymorphisms impact MAPT transcript levels and affect medial temporal lobe volume loss. When considered together with prior CSF 39–41, and imaging research 42–43, our findings suggest that data from GWAS, expression quantitative trait loci, and structural imaging measures may better elucidate underlying pathobiology than any of these markers by themselves. These results also demonstrate the utility of using entorhinal cortex and hippocampal atrophy rates as endophenotypes to identify and confirm AD risk variants.
