Alzheimer’s disease has always had its riddles and contradictions. For Pacific Northwest National Laboratory (PNNL) researcher Vladislav Petyuk, who has studied the progressive age-related disease spanning more than a decade, some of the difficulties come from study that “we can only connect one pair at a time.”
Petyuk’s research touches many fields in biology and Computational Science at PNNL. He has published dozens of publications on Alzheimer’s disease, and now he sees the needle in the right direction.
“Over the past 10 years,” says Petyuk, “research has shifted from a single drug target to a greater focus on proteins that play a role in cognitive resilience.”
Cognitive resilience is a measure of the brain’s ability to continue functioning even when the neuropathy of Alzheimer’s disease is high, which often causes the characteristic dementia. This means that in some people, the brain shows symptoms of the disease, but it does not affect the person’s ability to function. What makes some brains sensitive and some resilient, is an open question.
Petyuk recently collaborated with a multi-institutional team on a study that examined a large group of Alzheimer’s patients of more than 1800 people. The researchers have previously collected blood sample and brain tissue, along with large-scale data analytics to seek central themes in the early identification, prevention, and treatment of disease.
The results of the study, published in scientific advance, which helps to explain the progression of Alzheimer’s-related dementia in each patient. Furthermore, the findings outline a multilevel biological classification system that predicts disease severity and future neurological symptoms. “Evaluate the patient’s brain and blood proteinand other Biomoleculesreveal patterns that can then be targeted for tailored interventions,” Petyuk said.
The finding is particularly timely, as November is Alzheimer’s awareness month. In the United States, 5.4 million people age 65 and older live with Alzheimer’s disease. The numbers increase every year as the population ages.
Right tool, right time, right place
These types of large-scale studies, exploring proteins, and protein-related data are often referred to as proteomics studies.
Proteomics research at PNNL involves, among other things, the ability to analyze very large data sets. Examining, identifying and discovering proteins that can answer specific biological questions about their role in disease, as well as identify many new drug targets in the fight against Alzheimer’s disease and dementia related memory.
Leveraging the capabilities of PNNL’s advanced proteomics platform to answer these big questions in order to fill knowledge gaps, Petyuk has contributed to six studies published this year alone. The work confirms the power of discovery in the proteomics background at PNNL, as well as the strength in the collaborative efforts of Petyuk’s colleagues from around the world.
Assemble the pieces of the Alzheimer’s puzzle
Some symptoms of the disease are caused by the wrong combination of proteins. Protein needs to have a specific shape to work correctly, and just like baking, changing the recipe can lead to product distortion. Alzheimer’s disease can cause protein formulas to change. This study adds to an emerging pool of research into the proteins involved in the cognitive decline associated with the disease. These proteins can points to potential new targets for drug therapies.
Even with such a large amount of work, the puzzle has only been pieced together one piece at a time, with lots of smaller pieces that make sense, but a larger perspective remains unexplored. Petyuk, along with team leader Yasser Iturria-Medina at McGill University’s Montreal Neurological Institute, continues the work that helps us understand a complex and devastating disease. This promises new discoveries and new pieces to add to the Alzheimer’s puzzle.
Yasser Iturria-Medina et al, Unified epigenetic, transcriptional, proteomic and metabolic classification of Alzheimer’s disease progression and heterogeneity, scientific advance (2022). DOI: 10.1126/sciadv.abo6764
Pacific Northwest National Laboratory
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