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2019 Alzheimer's Association Clinician Scientist Fellowship (AACSF)

Study of tau strains to understand the phenotypic diversity in AD

Do different types of tau molecules determine how Alzheimer’s disease begins and progresses in different individuals?

Aurelien Lathuiliere, M.D., Ph.D.
Massachusetts General Hospital
Boston, MA - United States


Alzheimer’s is a progressive brain disease. There is a large variation in the rate of progression of Alzheimer’s in different individuals. In many instances, there is no single identifying characteristic with which Alzheimer’s manifests itself. Scientists are trying to obtain better understanding of the diversity in disease characteristics to develop tailor-made interventions and effective therapies.
Several neurodegenerative disorders such as Alzheimer’s, Progressive Supranuclear Palsy (PSP) etc. are associated with tau build-up, which can clump together to form tangles. These tangles form inside cells that eventually die. The tangles tend to spread throughout the brain as Alzheimer’s and related disorders progress. Recent studies have found that there may be several variations of tau that forms tangles. These  variations of tau appear to form different patterns of tangles in different Alzheimer’s brains — placing different areas of brain cells at risk.  Based on these findings, Dr. Aurelien Lathuiliere and colleagues suggest that variations in tau may be the underlying factor for why Alzheimer’s disease characteristics vary from one person to another.  

Research Plan

Dr. Lathuiliere will examine the role of different variations of tau in dementia. First, the researchers will refine a cutting-edge technology to isolate and measure tau activity in the brain tissue samples and cerebrospinal fluid (or the biological fluid surrounding the brain and spinal cord) from people who had different Alzheimer’s disease  characteristics. Using this method, Dr. Lathuiliere will determine if specific variations of accumulated tau are associated with certain Alzheimer’s disease characteristics. Finally, the researchers will test whether antibodies that target the different forms of tau may be used to prevent dementia forming tangles.


If successful, the study results could expand our knowledge of the underlying mechanisms of tau’s role in Alzheimer’s disease. Furthermore, the results could provide new avenues of potential therapies targeting tau.


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