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

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 (A beta). Here, we explored the association between regional A beta deposition, sociodemographic, and local biochemical factors. We quantified the A beta 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 A beta 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 A beta burden in the gray and white matter within each cortical region. We found higher A beta burdens in the TCx of AD octogenarians compared to CU ones. We also found higher A beta loads in the PCx of AD nonagenarians than in AD octogenarians. Moreover, AD women exhibited increased A beta deposition compared to CU women. Interestingly, we observed a negative correlation between education years and A beta burden in the white matter of both cortices in CU samples. In AD brains, the A beta 40, A beta 42, and pTau181 isoforms of A beta and Tau proteins were positively correlated with the A beta burden. Additionally, in the TCx of AD donors, the proinflammatory cytokine TNF alpha showed a positive correlation with the A beta 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.

Automated summary

This study explores the regional differences in A beta deposition in the brains of Alzheimer's disease (AD) patients and finds associations with age, gender, and education. Additionally, the study reveals correlations between A beta burden and inflammatory proteins.