Affection of Motor Network Regions by Tau Pathology Across the Alzheimer's Disease Spectrum

Stereotypical isocortical tau protein pathology along the Braak-Stages has been described as an instigator of neurodegeneration in Alzheimer's Disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the ADNI-cohort in patients with mild cognitive impairment (MCI; = 84) and dementia of the Alzheimer's Disease type (DAD; = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; = 26) were included. Standard-uptake ratio values (SUVR) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the effect of diagnostic disease category on tau pathology in the individual motor regions, controlling for age. We observed that tau pathology varies as a function of diagnostic category in predominantly higher motor regions (i.e., supplementary motor area, superior parietal lobe, angular gyrus and dorsal premotor cortex) compared to primary visual, sensory and motor regions. Indeed, tau in higher-order motor regions was significantly associated with decline in cognitive function. Together, these results expand our knowledge on the pattern of tau pathology in AD and suggest that higher motor regions are not spared from tau aggregation in the course of disease, potentially contributing to the symptomatic appearance of the disease. The presented data show relevant tau pathology in higher-order motor regions of patients with mild cognitive impairment (MCI) and dementia of the Alzheimer's Disease type (DAD), in a set of regions often neglected in the previous literature. Tau accumulation in higher-order motor regions was associated with clinical disease severity and increased cognitive dysfunction. These findings suggest that the concerted vulnerability of motor regions to tau pathology may contribute to motor/ praxis dysfunction observed in Alzheimer's Disease.