New research helps explain the progression of Alzheimer’s disease and predicts its severity

Alzheimer’s disease has always had its puzzles and contradictions. For Pacific Northwest National Laboratory (PNNL) researcher Vladislav Petyuk, whose research on age-related progressive disease spans more than a decade, some of the difficulties come from studies where “we can only connect the dots a pair at a time”.

Petyuk’s research touches multiple areas of biological and computational science at PNNL. He has produced dozens of publications on Alzheimer’s disease. But now she sees that the needle is moving in the right direction.

“Over the last 10 years,” Petyuk said, “research has moved away from a single drug target to focus more on proteins that have a role in cognitive resilience.”

Cognitive resilience is a measure of the brain’s ability to continue to function even with the high neuropathology of Alzheimer’s disease that would normally produce the characteristic dementia. This means that, in some people, the brain shows the symptoms of the disease, but it does not affect the person’s ability to function. What makes some brains sensitive and others resistant is an open question.

Petyuk recently collaborated with a multi-institutional team on a study that examined a large cohort of more than 1,800 people with Alzheimer’s disease. The researchers drew on previously collected blood and brain tissue samples, along with large-scale data analysis to search for themes central to the early identification, prevention, and treatment of the disease.

The research results published in Progress of science (November 2022), help explain the progression of Alzheimer’s-related dementia in each patient. Furthermore, the findings describe a multilevel biological classification system that predicts disease severity and future neurological symptoms. “Assessment of a patient’s brain and blood proteins, and other biological molecules, reveal patterns that can then be targeted for personalized intervention,” Petyuk said.

The discovery is particularly 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 grow annually as the population ages.

The right tools, at the right time, in the right place

These types of large-scale studies, which explore proteins and protein-related data, are often called proteomic studies.

Research in proteomics at PNNL involves, among other things, the ability to analyze very large data sets. The examination, identification and discovery of proteins can answer specific biological questions about their role in disease, as well as identify multiple 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 knowledge gaps, Petyuk has contributed to six research studies published this year alone. The work validates the power of discovery in the PNNL proteomics platform, as well as the power of 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 specific shape to function properly, and just like baking a cake, changing the recipe can result in a misshapen product. Alzheimer’s disease can cause protein recipes to change. This research adds to the emerging body of work on the proteins involved in cognitive decline that are associated with the disease. These proteins may indicate potential new targets for drug therapies.

Even with such a large body of work, the puzzle only comes together one piece at a time, with many smaller parts that make sense, but a bigger vista yet to be discovered. Petyuk, along with team leader Yasser Iturria-Medina at the McGill University Montreal Neurological Institute, continue work that adds to our understanding of a complex and devastating disease. This promises new discoveries and new pieces to add to the Alzheimer’s puzzle.

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