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2018 Alzheimer's Association Clinician Scientist Fellowship (AACSF)

Identification of tau seeds in the CSF of Alzheimer disease patients

Could detection of abnormal tau protein provide valuable diagnostic information about Alzheimer’s and other brain diseases?

Brian Hitt
UT Southwestern Medical Center
Dallas, TX - United States


In a healthy brain, the brain cell’s food transport system is organized in parallel strands like railroad tracks. These tracks allow food and nutrients to travel across the cell, feeding the cells and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s and other brain diseases like frontotemporal dementia, Pick’s disease etc. the shape of tau protein becomes modified leading to tau tangles and subsequent nerve cell damage. Researchers are trying to understand the underlying mechanisms of these processes.
Recent studies suggest that tau molecules become misshapen (or “misfolded”) in the earliest stages of Alzheimer’s and other brain diseases. Misfolded tau could act as harmful “seeds”, traveling to healthy cells that cause other tau molecules to become misshapen and clump together. Moreover, tau seeds appear to take on different shapes, and each shape (or “strain”) may have different effects on the brain.

Research Plan

Dr. Brian Hitt believes that targeting tau may be a way to halt the progression of Alzhiemer’s or other brain diseases. As a result, in preliminary studies, Dr. Hitt and colleagues have developed a method for detecting misshapen tau in the fluid that surrounds our brain and spinal cord - cerebrospinal fluid (CSF). To conduct his study, Dr. Hitt will collect CSF samples from participants with and without Alzheimer’s to determine if the samples contain abnormal or misshapen tau. The researchers will further study the samples to determine whether the CSF contains different shapes of tau and then investigate if specific forms of tau can be linked to the development of Alzheimer’s and other brain diseases.   


The results of this study could shed new light on the role of tau in Alzheimer’s and related dementias. It could also lay groundwork to identify how to measure different forms of tau in CSF to more accurately diagnose Alzheimer’s or other brain diseases.

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