Researchers understand that numerous proteins and pathways play a role in the emergence and advancement of neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia (FTD), and that these proteins can be found in the blood plasma of individuals affected by these conditions. However, it has been unclear which proteins are unique to each disease versus those that are common among two or more, complicating the diagnosis from blood samples and the creation of effective therapies.
A recent investigation by scholars at Washington University School of Medicine in St. Louis, published in Nature Medicine, sheds light on this issue. Directed by Carlos Cruchaga, the Barbara Burton & Reuben Morriss III Professor in the Psychiatry Department and head of the NeuroGenomics and Informatics Center at WashU Medicine, the researchers scrutinized protein activity in over 10,500 blood plasma samples from patients diagnosed with Alzheimer’s, Parkinson’s, or FTD. By investigating plasma proteins across all three disorders, the team — which also included Muhammad Ali, an assistant professor of psychiatry at WashU Medicine and the primary author of the study — successfully developed and validated models that forecasted the risk of each disease based on the irregularity of specific proteins.
In total, they discovered 5,187 proteins linked to Alzheimer’s, 3,748 to Parkinson’s, and 2,380 to FTD, which included several proteins not previously connected to neurodegenerative disorders.
Furthermore, they observed that over 1,000 proteins were associated with all three conditions — a surprisingly substantial number, as noted by Cruchaga. These shared proteins indicate common underlying processes and functions, particularly related to energy production and immune response, which could potentially be targeted in future treatments for neurodegenerative diseases overall.
Alzheimer’s, Parkinson’s, and FTD are recognized to overlap in both symptoms and pathological characteristics, Cruchaga pointed out; however, most investigations into the proteins and biomarkers associated with these diseases have concentrated on individual conditions, making it challenging to identify areas of overlap. Analyzing and comparing the protein landscape of Alzheimer’s, Parkinson’s, and FTD together was crucial for uncovering both common and disease-specific mechanisms.
This latest research builds upon earlier studies by Cruchaga and his team, who identified over 400 plasma proteins associated with Alzheimer’s disease. These recent findings may assist healthcare professionals in diagnosing complex cases or identifying neurodegenerative diseases at earlier stages, Cruchaga mentioned.
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