Researchers at WashU Medicine have uncovered new molecular insights into Alzheimer's disease, Parkinson's disease and other forms of dementia by analyzing thousands of proteins in both cerebrospinal fluid and blood plasma. The study, 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, represents one of the largest and most comprehensive multi-tissue analyses of proteins across multiple neurodegenerative diseases to date. The findings raise the possibility of developing blood tests for earlier and more precise diagnosis of these conditions.
In the study, published March 30 in Neuron, a multi-institutional team of clinicians, neuroscientists and data scientists, steered by Muhammad Ali, an assistant professor of psychiatry at WashU Medicine and first author of the study, analyzed nearly 7,000 proteins in samples of spinal fluid and blood from nearly 6,000 people - including people with neurodegenerative diseases as well as healthy controls - to better understand four major neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and frontotemporal dementia. By analyzing these diseases in parallel, the researchers could distinguish both shared and disease‑specific "molecular fingerprints." Across all four diseases, the protein analysis indicated clear evidence of inflammation, damage to the connections between nerve cells, and changes in the scaffolding around cells known as the extracellular matrix.
At the same time, the researchers discovered that each disease had its own distinctive patterns. Using these patterns, the team created computer models that could distinguish people with each disease from those without neurodegenerative disease with high accuracy - at least as good as some current gold‑standard tests, such as PET scans - based on their blood or spinal fluid samples. These models could be used to develop more precise diagnostic tests or to help monitor disease progression or patient response to treatment.
By revealing both shared and disease‑specific immune and structural changes, the study also indicates that some treatment strategies might be effective across several types of dementia - such as those treatments targeting chronic inflammation or the blood-brain barrier - while other therapies could be tailored to each disease.
