Structure of toxic tau aggregates determines type of dementia, rate of progression
The distinct structures of toxic protein aggregates that form in degenerating brains determine which type of dementia will occur, which regions of brain will be affected, and how quickly the disease will spread, according to a study from the Peter O’Donnell Jr. Brain Institute.
The research helps explain the diversity of dementias linked to tau protein aggregation, which destroys brain cells of patients with Alzheimer’s and other neurodegenerative syndromes. The study also has implications for earlier and more accurate diagnoses of various dementias through definition of the unique forms of tau associated with each.
“In addition to providing a framework to understand why patients develop different types of neurodegeneration, this work has promise for the development of drugs to treat specific neurodegenerative diseases, and for how to accurately diagnose them. The findings indicate that a one-size-fits-all strategy for therapy may not work, and that we have to approach clinical trials and drug development with an awareness of which forms of tau we are targeting,” said study author Dr. Marc Diamond, founding Director of the Center for Alzheimer’s and Neurodegenerative Diseases, and Professor of Neurology and Neurotherapeutics with the O’Donnell Brain Institute at UT Southwestern Medical Center.
Researchers used special cell systems to replicate distinct tau aggregate conformations. These different forms of pathological tau were then inoculated into the brains of mice. Each form created different pathological patterns, recapitulating the variation that occurs in diseases such as Alzheimer’s, frontotemporal dementias, and traumatic encephalopathy.
The different forms of tau caused pathology that spread at different rates through the brain, and affected specific brain regions. This experiment demonstrated that the structure of pathological tau aggregates alone is sufficient to account for most if not all the variation seen in human neurodegenerative diseases that are linked to this protein.
The finding could have a notable impact on widespread efforts at the O’Donnell Brain Institute and elsewhere to develop treatments that eliminate tau and other toxic proteins from the brains of dementia patients.
“The challenge for us now is to figure out how to rapidly and efficiently determine the forms of tau that are present in individual patients, and simultaneously, to develop specific therapies. This work says that it should be possible to predict patterns of disease in patients and responses to therapy based on knowledge of tau aggregate structure,” said Dr. Diamond, who holds the Distinguished Chair in Basic Brain Injury and Repair.
Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2016/oct/identifying-tau-strains.html
