Scientists know that many proteins and pathways are involved in the development and progression of neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia (FTD), and that these proteins can be detected in the plasma of people with the conditions. But it hasn't been clear exactly which proteins are distinct to one disease vs. shared among two or more of them, adding to the difficulty both of diagnosing these complex diseases from blood samples and of developing effective treatments.
A new study by Washington University School of Medicine in St. Louis researchers, published in Nature Medicine, provides some answers. Led by Carlos Cruchaga, the Barbara Burton & Reuben Morriss III Professor in the Department of Psychiatry and director of the NeuroGenomics and Informatics Center at WashU Medicine, the researchers analyzed protein activity in more than 10,500 blood plasma samples from patients with Alzheimer's disease, Parkinson's disease or FTD. By examining plasma proteins across all three conditions in the new study, the team - which also included Muhammad Ali, an assistant professor of psychiatry at WashU Medicine and first author of the study - was able to create and validate models that predicted the risk of each disease based on the dysregulation of certain proteins.
Altogether, they identified 5,187 proteins associated with Alzheimer's, 3,748 with Parkinson's and 2,380 with FTD, including a number of proteins not previously associated with neurodegenerative diseases.
They also found that more than 1,000 proteins were associated with all three diseases - an unexpectedly large amount, Cruchaga noted. These shared proteins point to common processes and functions, primarily involving energy production and immune response, that could be leveraged in the future to treat neurodegenerative diseases in general.
Alzheimer's disease, Parkinson's disease and FTD are known to overlap both in their symptoms and in their pathological features, Cruchaga noted; yet most studies of the proteins and biomarkers involved in these diseases have focused on a single condition, which has made it difficult to determine where they do and don't overlap. Studying and comparing the protein landscape of Alzheimer's, Parkinson's and FTD together was instrumental to identify common and disease-specific disease mechanisms.
The current research builds on previous work by Cruchaga and his team in which they found more than 400 plasma proteins associated with Alzheimer's disease. The new findings may help physicians diagnose complex cases or detect neurodegenerative diseases at an earlier stage, Cruchaga said.
