Project Overview

In Alzheimer’s disease (AD), the pathogenic amyloid-β (Aβ) peptide accumulates in the brain parenchyma and in vessel walls. Deposition of Aβ in the brain vasculature, known as cerebral amyloid angiopathy (CAA), can lead to brain hemorrhages. Up to 90% of AD patients develop CAA, with different degrees of severity. Patients with abundant vascular Aβ deposition are at increased risk of developing severe side effects upon treatment with the newly approved immunotherapies.

A diagnosis of CAA is based on costly and not easily accessible MRI scans. Also, the sensitivity and specificity of such techniques are suboptimal. Currently, clinicians cannot estimate the amount of CAA pathology in AD patients by routine analyses, nor can they predict which patients are at risk of severe side effects from immunotherapy. We aim to develop a novel diagnostic tool for detecting and estimating the extent of CAA by analyzing cerebrospinalfluid (CSF).

Pathogenic proteins, such as Aβ, can transmit their toxic conformations to physiological protein forms, a process called “seeding.” Diagnostic tools measuring such seeding behaviours have been developed for other neurodegenerative diseases, but none are currently available for Aβ. Using tracers that can preferentially detect pathogenic proteins deriving from the brain vessels, we aim to develop a CSF-based assay that could discriminate between patients with and without CAA.

If successful, our assay will allow for a more accurate and accessible method to diagnose CAA. Such a diagnostic tool would significantly affect the clinical management of our patients. In addition to aiding clinicians to choose the most appropriate treatments, it could allow for a more appropriate selection of patients for clinical trials, thus impacting the outcome of such assessments.

Our goal is to develop a tool to analyze cerebrospinal fluid that will help physicians understand if and how brain vessels are affected in the brain of patients with Alzheimer’s disease. This knowledge can help them to choose the most appropriate treatment and thereby increase the likelihood for a successful treatment outcome, while minimizing the risk for adverse side effects.

Principal Investigator

Martin Ingelsson , University Health Network

Partners and Donors

Alzheimer Society of Canada