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2019 Biomarkers Across Neurodegenerative Diseases Grant (BAND)

Tau and alpha-synuclein oligomers: Cognitive predictors in synucleinopathy

Could measuring collections of a few misfolded proteins in a biological fluid predict brain diseases?


Alice Chen-Plotkin, M.D.
University of Pennsylvania
Philadelphia, PA - United States


The brain cell’s energy and nutrient transport system is organized in parallel strands like railroad tracks. These tracks allow nutrients to travel across the cell, delivering key materials to the cells, providing them with energy and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s and other brain diseases like frontotemporal dementia, Parkinson’s disease and Pick’s disease the shape of tau protein becomes modified and this could contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage.
Similarly, a protein called alpha-synuclein is thought to help in maintaining proper nerve cell communication in the brain. However, misfolded collections of alpha-synuclein within nerve cells are hallmarks of brain diseases such as Parkinson’s disease and Dementia with Lewy Bodies (DLB). Studies show that both misfolded alpha-synuclein and tau can sometimes be found together in the brain tissue of individuals with Parkinson’s disease and DLB.  Dr. Alice Chen-Plotkin and colleagues will determine if there is cross talk between these misfolded proteins and if it accelerates brain changes seen in these brain disorders.

Research Plan

The researchers will conduct their study on 500 individuals including those with Parkinson’s, DLB, frontotemporal dementia as well as cognitively unimpaired people. Dr. Alice Chen-Plotkin and her team have developed a method to measure small collections of a few molecules (called “oligomers”) of protein composed of 1) only alpha synuclein 2) only tau and 3) a combination of both tau and alpha-synuclein. The method called sFIDA (surface-based fluorescence intensity analysis) uses antibodies as well as laser-based scans to measure these different types of collections of molecules. Dr. Plotkin believes that measuring these collections in a biological fluid surrounding the brain and spinal cord (called the cerebrospinal fluid or CSF) may reflect an underlying disease process and could be a biological marker for individuals with Parkinson’s disease and DLB.
In addition, the researchers will also determine genetic changes that may predict levels of each type of these 3 collections of molecules in the CSF from individuals with and without the brain disease.


If successful, the study results could be used to predict brain diseases.

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