Age-related dementias are reaching epidemic levels, affecting over 600,000 Canadians. The most common cause of age-related dementia is Alzheimer’s disease (AD). The defining pathology of AD is the build-up of abnormal forms of two proteins in the brain, amyloid and tau. The majority of people with a diagnosis of AD, however, do not only have abnormal build-up of amyloid and tau in the brain, but also experience damage to the brain’s blood vessels, or cerebrovasculature.

Cerebrovascular damage adds directly to AD clinical symptoms, and can also worsen the amyloid and tau pathology. This complicates diagnosing AD and finding effective treatments. Cerebrovascular damage in AD can be assessed using magnetic resonance imaging (MRI), a non-invasive brain scanning technique, but is costly. Our study goal is to distinguish between low and high burden of cerebrovascular damage in AD by establishing ‘signatures’ of different proteins that could be assessed from a blood sample.

To establish these protein signatures we will analyze packets of material in “endothelial-secreted-extracellular-vesicles” (EEVs), especially those released by the cerebrovasculature into blood. Unlike previous studies, we will use mass-spectrometry technique to analyze EEV proteins, and compare levels in people with and without AD, and with different amounts of cerebrovascular damage on MRI. We have identified several proteins linked to cerebrovascular function that we expect to differ between groups, according to their level of cerebrovascular damage.

Once established, protein-signatures of low and high cerebrovascular damage in AD obtained from circulating EEVs can serve as minimally-invasive blood biomarkers. Given that cerebrovascular damage is common in AD, availability of blood biomarkers will improve AD diagnosis and enable more targeted treatment strategies. Such biomarkers could also serve as efficacy measures in clinical trials of drugs targeting the vascular component of AD, which may be more amenable to treatment than the neurodegenerative component of AD.

Brain vascular damage is frequently present in AD and worsens clinical symptoms. The goal of our project is to identify blood biomarkers of cerebrovascular damage, which are notably absent in AD. Blood biomarkers, once identified and established, can serve as (1) a cost-effective, widely accessible tool in the workup of AD, and help orient other tests (e.g., neuroimaging) with reduced availability, and (2) aid in the prediction and monitoring of therapeutic effects of drugs.