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

Abstract

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 Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort in patients with mild cognitive impairment (MCI; N = 84) and dementia of the Alzheimer's disease type (DAD; N = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N = 26) were included. Standard uptake ratio values (SUVRs) 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 in vivo 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.

Keywords: Alzheimer's disease; mild cognitive impairment; motor regions; positron emission tomography; regional tau burden.

Figure 1.

Set of probabilistic regions-of interest (ROIs) used. Cytoarchitectonically regions inferred from the SPM Anatomy toolbox are overlayed on a structural template image in MNI-space using CAT toolbox. L, left hemisphere, R, right hemisphere, ROIs, regions of interest. Colors indicate different label number within the probabilistic motor ROIs, which are exemplary color coded on the right hemisphere.

Figure 2.

Association of tau pathology in higher-order motor regions with disease category. The mean tau SUVRs for the nine regions are shown collapsed over both hemispheres. The graphs illustrate the significant region × group interaction, since a significant group effect for the mean tau SUVRs was observed in four regions (SMA, supplementary motor area; AG, angular gyrus; SPL, superior parietal lobe; and DPMC, dorsal premotor cortex), while the tau SUVRs did not differ significantly between the three groups in the other five regions (primary motor, area MT/V5, supramarginal gyrus, primary sensory, and primary visual). HC, healthy controls; MCI, mild cognitive impairment; DAD, dementia of the Alzheimer's disease type. * Indicates p < 0.05 for the planned post hoc comparisons employing t tests.

Figure 3.

Correlation between tau pathology in higher-order motor regions and cognitive dysfunction. Displayed are correlation coefficients from the partial correlation analysis, examining tau pathology in motor regions and performance on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13) for all participants (n = 135). SMA, supplementary motor area.