Progression of Tau Pathology in Non-Amnestic Alzheimer's Disease




Assistant Professor of Neurology

Project Summary

During the PURM program, I worked at the Hospital of the University of Pennsylvania in the Frontotemporal Degeneration Center under Dr. David Irwin. The basis of my research there was studying the differences between Alzheimer’s Disease (AD) and a variant of AD known as non-amnestic Alzheimer’s Disease. This variant’s symptoms varied mainly in its lack of episodic memory loss, which is usually associated with AD, and is diagnosed as another disorder until death, when the brain is autopsied and the AD pathology is found. Typical Alzheimer’s follows a set progression within the brain, so we hypothesized that, due to the lack of episodic memory loss, the AD progression would be in reverse in non-amnestic AD, with the least tau protein pathology in the hippocampus.

To study this, brain tissue from the four specific regions of the brain were sampled for tau pathology and compared by non-amnestic vs typical AD and by specific pre-death disorder vs typical AD. The tissue was imaged and then randomly sampled within a specific cortex of the region using a program known as HALO. After specific regions of interest were drawn, HALO would analyze a specific stain of tau protein and measure the concentration of the protein by the thickness of the stain. This was converted into a percent area occupied by the protein, allowing a direct comparison between cases.

Using this percent area occupied, non-amnestic and typical AD could be measured and compared to find any meaningful results. While the data itself did not show a large amount of significant values, the hippocampal hypothesis was very off. This was peculiar, especially due to the massive differences in memory function between the two types of Alzheimer’s Disease. We then decided to study specific parts of the hippocampal memory making pathway and compare the non-amnestic vs typical AD tau pathology within. I am planning to continue this project during my time at Penn, as well as write a thesis with Dr. Irwin on this specific topic of neurology.

Progression of Tau Pathology in Non-Amnestic Alzheimer's Disease