Neuropathological and sociodemographic factors associated with the cortical amyloid load in aging and Alzheimer's disease.

ABSTRACT

Alzheimer's disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive abilities. A pathological hallmark of AD is a region-specific accumulation of the amyloid-beta protein (Aß). Here, we explored the association between regional Aß deposition, sociodemographic, and local biochemical factors. We quantified the Aß burden in postmortem cortical samples from parietal (PCx) and temporal (TCx) regions of 27 cognitively unimpaired (CU) and 15 AD donors, aged 78-100 + years. Histological images of Aß immunohistochemistry and local concentrations of pathological and inflammatory proteins were obtained at the "Aging, Dementia and TBI Study" open database. We used the area fraction fractionator stereological methodology to quantify the Aß burden in the gray and white matter within each cortical region. We found higher Aß burdens in the TCx of AD octogenarians compared to CU ones. We also found higher Aß loads in the PCx of AD nonagenarians than in AD octogenarians. Moreover, AD women exhibited increased Aß deposition compared to CU women. Interestingly, we observed a negative correlation between education years and Aß burden in the white matter of both cortices in CU samples. In AD brains, the Aß40, Aß42, and pTau181 isoforms of Aß and Tau proteins were positively correlated with the Aß burden. Additionally, in the TCx of AD donors, the proinflammatory cytokine TNFα showed a positive correlation with the Aß load. These novel findings contribute to understanding the interplay between sociodemographic characteristics, local inflammatory signaling, and the development of AD-related pathology in the cerebral cortex.