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Proteomic associations with brain and cognitive health and their interactions with modifiable risk factors for dementia

Project ongoing

Project Overview

As people live longer, our society undergoes rapid demographic change. Dementia and cognitive impairment in older adults poses a greater challenge to our healthcare system, affecting patients and caregivers. Identifying dementia early is critical to provide treatment that can slow or stop the disease.

We know that early signs of dementia in the brain include subtle changes in gray and white matter and communication between different parts of the brain, alongside changes in cognitive performance that is distinct from healthy aging. However, two questions remain: (1) what are the biological pathways leading to these early signs of dementia, alongside the traditional amyloid and tau mechanisms? (2) Can we find blood tests that can serve as markers of worse brain and cognitive health?

This study aims to use large-scale proteomic data from different datasets from the UK (3000 proteins) and the US (7000 proteins) with over 6,000 people in total to answer these questions. We will identify relationships between blood protein levels and several measures of brain health from MRI as well as cognitive performance. We will then test whether some of these relationships are sex-specific, and whether people with treatable conditions like cardiovascular disease, depression or with high BMI and cholesterol have unique proteomic markers of brain and cognitive health.

As a result, we expect to clarify which sets of proteins predict worse brain and cognitive outcomes, potentially generating inexpensive markers for more specialized MRI and cognitive tests. Understanding the genetic associations between proteomic data and MRI will help disentangle the contributions of different biological pathways and environmental factors to brain circuits underlying dementia risk.

Partners and Donors

Canadian Institutes of Health Research (CIHR)