Alzheimer’s disease has always had its riddles and contradictions. For Vladislav Petyuk, a researcher at the Pacific Northwest National Laboratory (PNNL) whose research on progressive, age-related disease has spanned over a decade, some of the struggles stem from studies where «we can only connect the dots one pair at a time.»
Petyuk’s research touches many areas in biological and computational science at PNNL. He has produced dozens of publications on Alzheimer’s disease. But now he sees the needle moving in the right direction.
«Over the last 10 years,» Petyuk said, «research has moved from a single drug target to a greater focus on proteins that have a role in cognitive resilience.»
Cognitive resilience is a measure of the brain’s ability to continue functioning even with the high level of Alzheimer’s disease neuropathology that normally causes the hallmark of dementia. This means that in some people the brain shows symptoms of the disease but does not affect the person’s functions. What makes some brains sensitive and others flexible is an open question.
Petyuk recently collaborated with a multi-institutional team on a study that examined a large Alzheimer’s disease cohort of more than 1,800 people. The researchers drew on large-scale data analysis, along with previously collected blood samples and brain tissue, to explore central themes in the early diagnosis, prevention and treatment of the disease.
Research findings published Science Advances (November 2022) helps explain the progression of Alzheimer’s-related dementia in each patient. In addition, the findings outline a multilevel biological classification system that predicts disease severity and future neurological symptoms. «Evaluation of a patient’s brain and blood proteins and other biological molecules reveals patterns that can then be targeted for specific intervention,» Petyuk said.
The discovery is particularly timely, as November is Alzheimer’s disease awareness month. In the United States, 5.4 million people aged 65 and older are living with Alzheimer’s disease. Their numbers increase each year as the population ages.
The right tools, at the right time, in the right place
Such large-scale studies investigating proteins and protein-related data are often referred to as proteomic studies.
Proteomics research at PNNL includes, among other things, the ability to analyze very large datasets. Studying, identifying, and discovering proteins could help answer specific biological questions about their role in disease, as well as identify numerous new drug targets in the fight against Alzheimer’s disease and related dementia.
Leveraging PNNL’s advanced proteomics platform capabilities to answer these big questions to fill knowledge gaps, Petyuk contributed six research studies published this year alone. The study confirms the power of discovery in the proteomics platform at PNNL and the strength in the collaborative efforts of Petyuk’s colleagues from around the world.
Putting the pieces of the Alzheimer’s puzzle together
Some symptoms of the disease are due to misfolding of proteins. Proteins need to have a certain shape to work properly, and just like baking a cake, changing the recipe can cause the product to become deformed. Alzheimer’s disease can cause protein prescriptions to change. This research adds to emerging studies on proteins involved in disease-related cognitive decline. These proteins may represent potential new targets for drug therapies.
Even with such a large body of work, the puzzle is only put together one piece at a time, with many small pieces that make sense, but a larger view yet to be explored. Petyuk continues work with team leader Yasser Iturria-Medina at McGill University’s Montreal Neurological Institute that contributes to our understanding of a complex and devastating disease. This promises new discoveries and new pieces to add to the Alzheimer’s disease puzzle.
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