Effects of MAPT rs17649553 on Structural Network Integrity and Verbal Memory in Parkinson's Disease

BackgroundCurrently, over 90 genetic loci have been found to be associated with Parkinsons disease (PD) in genome-wide association studies, nevertheless, the effects of these genetic variants on the clinical features and brain structure of PD patients are largely unknown. ObjectiveThis study investigated the effects of microtubule-associated protein tau (MAPT), rs17649553 (C>T), a genetic variant associated with reduced PD risk, on the functional and structural networks of PD patients. MethodsTotally 83 PD subjects from Parkinsons Progression Markers Initiative database were included for this study. They all received structural and functional magnetic resonance imaging and whole exome sequencing. The effects of MAPT rs17649553 on brain structural and functional networks were systematically assessed. ResultsMAPT rs17649553 T allele was associated with better verbal memory in PD patients. In addition, MAPT rs17649553 significantly reshaped the topology of gray matter covariance network and white matter network but not that of functional network. Both the network metrics in gray matter covariance network and white matter network were correlated with verbal memory, however, the mediation analysis showed that it was the small-worldness topology in white matter network that mediated the effects of MAPT rs17649553 on verbal memory. ConclusionIn sum, we proposed that MAPT rs17649553 T allele was associated with superior structural network topology and better verbal memory in PD. Future studies are needed to determine the role of MAPT rs17649553 in PD initiation and progression.