Here we report studies of the burden of neurodegenerative neuropathologies in a cohort of Medical Examiner (ME) subjects from the County of Santa Clara (California) to determine if this unique population of decedents manifested evidence of neurodegeneration that might underlie causes of death seen in an ME practice. We found that 13% of the brains from ME cases showed significant tau pathology, including 55% of those 65 years old and older and 63% of those 70 years old and older. The histochemical and immunohistochemical findings were consistent with Alzheimer's disease (AD) in 7 subjects and frontotemporal lobar degeneration (FTLD) tauopathy type in six cases. There were no cases of Parkinson's disease, dementia with Lewy Bodies or other neurodegenerative conditions. Our study suggests that decedents >65 years of age in an ME practice are afflicted by common causes of dementia such as AD and FTLD which could contribute wholly or in part to their causes of death.

Background: Synergies between amyloid-β (Aβ), tau, and neurodegeneration persist along the Alzheimer's disease (AD) continuum. This study aimed to evaluate the extent of spatial coupling between tau and neurodegeneration (atrophy) and its relation to Aβ positivity in mild cognitive impairment (MCI). Methods: Data from 409 subjects were included (95 cognitively normal controls, 158 Aβ positive (Aβ+) MCI, and 156 Aβ negative (Aβ-) MCI) Florbetapir PET, Flortaucipir PET, and structural MRI were used as biomarkers for Aβ, tau and atrophy, respectively. Individual correlation matrices for tau load and atrophy were used to layer a multilayer network, with separate layers for tau and atrophy. A measure of coupling between corresponding regions of interest/nodes in the tau and atrophy layers was computed, as a function of Aβ positivity. The extent to which tau-atrophy coupling mediated associations between Aβ burden and cognitive decline was also evaluated. Results: Heightened coupling between tau and atrophy in Aβ+ MCI was found primarily in the entorhinal and hippocampal regions (i.e., in regions corresponding to Braak stages I/II), and to a lesser extent in limbic and neocortical regions (i.e., corresponding to later Braak stages). Coupling strengths in the right middle temporal and inferior temporal gyri mediated the association between Aβ burden and cognition in this sample. Conclusions: Higher coupling between tau and atrophy in Aβ+ MCI is primarily evident in regions corresponding to early Braak stages and relates to overall cognitive decline. Coupling in neocortical regions is more restricted in MCI.