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2022 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Glial signatures of tau propagation in Alzheimer's disease

How do genes and proteins in different types of brain cells impact Alzheimer’s-related tau accumulation?

Bruna Bellaver, Ph.D.
University of Pittsburgh
Pittsburgh, PA - United States


Alzheimer’s is associated with specific brain changes, including the accumulation of beta-amyloid and tau proteins into abnormal plaques and tangles, respectively. These protein clumps may hinder nerve cell function in the brain during Alzheimer’s and lead to nerve cell death. Because plaques and tangles often appear together in the Alzheimer’s brain, scientists have been exploring how amyloid and tau production are linked. 

According to some studies, tau tangle accumulation is often dependent on the presence of beta-amyloid plaques. Other studies, however, have found that in many individuals, including those with mild cognitive impairment (or MCI, a condition of subtle memory loss that may precede Alzheimer’s), tau accumulation takes place in the brain without beta-amyloid. These findings suggest the need to examine the mechanisms underlying different types of tau accumulation – those that are linked with beta-amyloid and those that are not.

Research Plan

In initial studies with brain tissue from Alzheimer’s-like mice, Dr. Bruna Bellaver and colleagues examined the role of glial cells in tau and beta-amyloid build-up. Glial cells include microglia (the brain’s primary immune cells) and astrocytes (a type of helper cell in the brain). The researchers found that variations in genes and gene activity among the glial cells were related to differences in how tau and beta-amyloid form tangles and plaques.  

Dr. Bellaver’s team will now conduct a larger study of the links between glial cells and Alzheimer’s-related tau and beta-amyloid. Using brain tissue from individuals who had MCI, the researchers will identify and analyze the “transcriptome” (or collection of all gene readouts) and “proteome” (or collection of all proteins) in different astrocyte and microglial cells. This work will clarify how specific glial cell genes – and the proteins produced from those genes – impact tau production that is either related to or not related to beta-amyloid clumping. The researchers will then examine blood samples from the same group of brain tissue, in order to determine blood levels of glial proteins linked to tau accumulation with and without beta-amyloid.     


Results from this project could clarify the different ways that tau and beta-amyloid can accumulate in Alzheimer’s disease, and how glial cells play a role in those differences. It could also lead to novel blood tests and other measures for diagnosing Alzheimer’s at an early stage.

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