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2017 Grants - Zanier
Prion-Like Tauopathy in Post-Traumatic Alzheimer's Disease
Elisa Zanier, M.D.
Pharmacological Research Institute Mario Negri
2017 Alzheimer's Association Research Grant (AARG)
How does traumatic brain injury progress to Alzheimer's disease?
In recent years, it has been recognized that traumatic brain injury — such as what may occur in automobile accidents or with repeated blows to the head — is a risk factor for Alzheimer's disease. Traumatic brain injury is associated with accumulation of the protein tau in the brain. Accumulation of tau in the brain is also a characteristic feature of Alzheimer's disease.
Research has also shown that when tau accumulates in one brain region, it tends to spread from there to other brain regions. This pattern of spread resembles what occurs in some other brain diseases associated with molecules known as prions. Prions are protein fragments that cause malfunction of other proteins and slowly propagate through the brain, causing neurodegeneration. Thus, it has been proposed that tau from a traumatic injury in one region of the brain may behave like a prion, spreading through the brain and eventually causing Alzheimer's disease.
Elisa Zanier, M.D., and colleagues have proposed a series of experiments to test the idea that tau behaves like a prion in people with traumatic brain injury, eventually leading to the development of Alzheimer's disease. The researchers plan to study mice that have been genetically altered to have an Alzheimer's-like condition. Dr. Zanier's team will study how traumatic brain injury produces different versions of tau that behave like prions. They will inject different tau strains into the brain of their model mice to determine how different versions of tau produce Alzheimer's-like brain changes, and whether those brain changes spread to other regions of the brain.
These studies will provide new information about how traumatic brain injury increases the risk of Alzheimer disease. This will also allow scientists to determine if strategies targeting tau propagation may be effective at preventing the development of Alzheimer's disease in people who have had a traumatic brain injury.