Development of a diagnostic amyloid-β seed amplification assay to discriminate between Alzheimer’s disease with and without cerebral amyloid angiopathy
In Alzheimer’s disease (AD), the pathogenic amyloid-beta protein accumulates in the brain parenchyma and vessel walls. Deposition of amyloid-beta in the brain vasculature can lead to brain hemorrhages. Also, patients with abundant vascular amyloid-beta deposition are at increased risk of developing severe side effects upon treatment with the newly approved immunotherapies. Currently, clinicians cannot estimate the amount of vascular pathology in AD patients by routine analyses. Pathogenic proteins, such as amyloid-beta, can transmit their toxic conformations to physiological protein forms, a process called “seeding.” We aim to develop a assay that can analyse seeding characteristics of amyloid-beta and thereby discriminate between patients with and without vascular pathology. Such a diagnostic tool would significantly affect the clinical management of our patients. In addition to aiding clinicians in choosing the most appropriate treatments, it could allow for a more appropriate selection of patients for clinical trials.
