New research helps explain Alzheimer’s disease progression and predict its severity – ScienceDaily

Alzheimer’s disease has always had its mysteries and contradictions. For Pacific Northwest National Laboratory (PNNL) researcher Vladislav Petyuk, whose research on the progressive age-related disease spans a decade, some of the problems stem from studies where “we can only connect the dots in pairs.”

Petyuk’s research touches on several areas of life and computational science at PNNL. He has authored dozens of publications on Alzheimer’s disease. But now he sees that the needle is moving in the right direction.

“Over the past 10 years,” Petyuk said, “research has moved away from a single drug target and has focused more on the proteins that play a role in cognitive resilience.”

Cognitive resilience is a measure of the brain’s ability to continue functioning even in the high neuropathology of Alzheimer’s disease, which would normally produce the characteristic dementia. This means that in some people the brain will show the symptoms of the disease but the person’s ability to function will not be affected. What makes some brains sensitive and others resilient is an open question.

Petyuk recently worked with a multi-agency team on a study that looked at a large Alzheimer’s disease cohort of over 1,800 people. The researchers used previously collected blood samples and brain tissue, as well as extensive data analysis, to look for key issues in the early detection, prevention and treatment of the disease.

The research results are published in scientific advances (November 2022) help explain the progression of Alzheimer’s-related dementia in each patient. In addition, the results outline a multi-level biological classification system that predicts disease severity and future neurological symptoms. “Assessment of a patient’s brain and blood proteins and other biological molecules reveals patterns that can then be targeted for tailored intervention,” Petyuk said.

The discovery comes especially timely as November is Alzheimer’s Disease Awareness Month. In the United States, 5.4 million people age 65 and older are living with Alzheimer’s disease. The numbers are increasing annually as the population ages.

The right tools at the right time in the right place

These types of large-scale studies that examine proteins and protein-related data are often referred to as proteomics studies.

Proteomics research at PNNL includes, among other things, the ability to analyze very large data sets. The study, identification and discovery of proteins can answer specific biological questions about their role in the disease and identify several new drug targets in the fight against Alzheimer’s disease and related dementias.

Leveraging the capabilities of PNNL’s advanced proteomics platform to answer these big questions and fill in the knowledge gaps, Petyuk has contributed to six published research studies this year alone. The work validates the discovery power of the proteomics platform at PNNL, as well as the power of the collaborative efforts of Petyuk’s colleagues from around the world.

Put the pieces of the Alzheimer’s puzzle together

Some symptoms of the disease are due to the misfolding of proteins. Proteins need to be in a specific shape to function properly, and much like baking a cake, changing the recipe can result in a misshapen product. Alzheimer’s disease can cause protein recipes to change. This research complements emerging work on proteins involved in cognitive decline and associated with the disease. These proteins could point to potential new targets for drug therapies.

Even with a work this large, the puzzle is still just being pieced together piece by piece, with many smaller pieces that make sense but a larger view yet to be discovered. Petyuk, along with team leader Yasser Iturria-Medina at McGill University’s Montreal Neurological Institute, continues work contributing 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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