Regional Variability of Pathology-Associated Properties of Tau in Posterior Cortical Atrophy

2022, 2023

Alzheimer’s disease (AD) typically manifests first with short-term memory problems. However, in less common circumstances, AD can start with cognitive symptoms other than memory deficits. Posterior cortical atrophy (PCA) is a less common form of AD that starts with changes in visual perception and/or spatial awareness rather than memory loss. Although typical AD and PCA AD have different symptoms, both conditions have the same pathological hallmarks of amyloid beta plaques and tau-containing tangles. However, the tau proteins tend to accumulate in different regions of the brain in PCA AD compared with typical AD, which are the regions that serve visual functions (posterior cortical areas) or memory functions (e.g., the hippocampus), respectively. Why does this happen? We postulate that tau in PCA AD differs from tau in typical AD at the molecular level, perhaps leading it to be predisposed to affect the posterior cortical regions rather than the hippocampus. We and others have developed methods to study the characteristics of pathological tau in typical AD, but these techniques have not been applied to asking about tau in PCA AD. This project aims to examine three characteristics of tau in key brain regions in PCA AD compared with typical AD: 1) the distribution of pathological tau in different brain regions, 2) the ability of pathological tau to provide a template for further tau aggregation, and 3) the patterns of protein modifications on the tau protein. Investigating these characteristics of pathological tau in PCA AD will enhance our understanding of the disease-related changes in the brain that occur in PCA AD. This study also will provide deeper insights into the differences in tau at the molecular level in PCA AD compared with typical AD. Overall, the knowledge gained through this project will expand our understanding of the disease process that occurs in PCA AD, and may suggest new avenues for treatment if we uncover unique molecular aspects of tau in PCA AD that can be targeted.

Funding to Date



Studies of Tau, Translational


Bradley T. Hyman, M.D., Ph.D.

John R. Dickson, M.D., Ph.D.