2022 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Cross-seeding Between Bacterial and Mammalian Amyloids.

How might bacterial infections be associated with misfolded proteins in brain disorders?

Rodrigo Morales, Ph.D.
University of Texas Health Science Center at Houston
Houston, TX - United States

Background

Several brain disorders, including Alzheimer’s and Parkinson’s disease, are characterized by abnormal proteins in the brain. These proteins accumulate into clumps that can damage brain cell health and function. The two major hallmarks of Alzheimer’s are beta-amyloid plaques and the abnormal form of the tau protein forming tau tangles. A different protein called alpha-synuclein misfolds and forms clumps in the brain common in Parkinson’s disease but is also seen in Alzheimer’s. Scientists do not yet fully understand the biological mechanisms regarding how protein misfolding occurs. Misfolded proteins could act as harmful “seeds,” traveling to healthy cells and causing other protein molecules to become misshapen and clump together. 

Studies have shown that disease-causing bacteria, as well as the bacteria living in our gut, make amyloid proteins that are biologically similar to human proteins. Dr. Rodrigo Morales and colleagues believe that misfolded proteins created from bacteria may act as seeds and cause the misfolding and aggregation of proteins in human-related systems. It is possible that bacterial infection could contribute to the development or progression of diseases such as Alzheimer’s and Parkinson’s disease. Currently, whether and how misfolded amyloid proteins from bacteria play a role in neurodegeneration is unknown.

Research Plan

Dr. Morales and colleagues will study the interactions between proteins from bacteria and proteins from mammals in two ways: in cellular models of Alzheimer’s in a laboratory dish and by injecting amyloid proteins from bacteria into genetically engineered Alzheimer’s-like mice. The researchers will study whether and how bacterial proteins can induce the formation of misfolded aggregates of amyloid-beta, tau, and alpha synuclein. They will also investigate the impact of bacterial proteins on brain cell health and inflammation.

Impact

If successful, the findings may shed light on a new factor — bacterial infections — that contributes to the development and progression of neurodegenerative disorders, including Alzheimer’s.