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2019 Biomarkers Across Neurodegenerative Diseases Grant (BAND)

Comparing Novel Biomarkers in Alzheimer and Parkinson Diseases

Do certain proteins linked to Alzheimer’s and Parkinson’s disease interact to promote cognitive changes?
 

Brian Gordon, Ph.D.
Washington University in St.Louis
St. Louis, MO - United States



Background

Alzheimer’s disease and Parkinson’s  are often associated with certain characteristics that sometimes appear specific to each disease— loss of memory and other cognitive functions in Alzheimer’s and problems with movement in Parkinson’s. However, studies show that both disorders, may have an overlap of  variety of  characteristics. Individuals with Parkinson’s often have problems with cognition, and both diseases can increase one’s risk for hallucinations and delusions. Both disorders may also share certain biological markers (or biomarkers) at the molecular level, including clumping of multiple types of protein in the brain causing damage to brain cells. The beta-amyloid protein forms clumps known as beta-amyloid plaques, a hallmark of Alzheimer’s disease. Another protein known as alpha-synuclein loses its normal shape and clumps together in the brain (called Lewy bodies), characteristic of individuals with Parkinson’s disease. Nonetheless, many individuals with Alzheimer’s or Parkinson’s may develop both plaques and Lewy bodies in their brain. Studies suggest that beta-amyloid and alpha-synuclein may interact  with one another, impacting the formation and progression of disease.
 

Research Plan

Dr. Brian Gordon and colleagues will examine the interplay between multiple biomarkers of brain diseases  and their impact on brain health. First, the researchers  will measure beta-amyloid and alpha-synuclein levels in people who have (1) early-stage Alzheimer’s, (2) early-stage Parkinson’s disease, (3) later stage Parkinson’s or (4) no cognitive impairment. This effort will utilize brain data, CSF and blood samples from participants in ongoing studies of both diseases. The researchers will then examine whether individuals with high levels of beta-amyloid and alpha-synuclein are more likely to develop cognitive problems and dementia, and whether this increased risk may be linked to interactions between these proteins.
 
In addition, Dr. Gordon and colleagues will explore another potential marker of disease called neurofilament light chain (NfL). Neurofilaments are proteins that make up the nerve cell structure. These proteins get dispersed in the CSF and blood after the nerve cells die. Recent studies have found that NfL levels may become abnormally high in a variety of brain disorders. Dr. Gordon’s team will measure NfL content in the CSF and blood samples to determine if elevated levels are linked to cognitive changes in early Alzheimer’s and Parkinson’s disease.    

Impact

The study results could refine our understanding of how protein interactions impact a variety of brain disorders. They could also lead to improved methods of diagnosing such disorders at an early stage.
 

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