Discovery and validation of biomarkers of autoimmunity in Alzheimer's Disease.

Sinai Health System, Toronto ON

Investigators

Abstract

R21 Project summary abstract Alzheimer’s disease is a serious neurodegenerative disorder affecting millions of people. Currently there are no effective therapies and the reliance on managing the disease depends on accurate diagnosis and assessment of progression. In our grant application we aim to identify biomarkers for differential diagnosis between Alzheimer’s disease and other neurodegenerative disorders and also, biomarkers that are able to non-invasively assess the progression of the disease. We postulate that Alzheimer’s disease is pathogenesis is multifactorial and includes the classical amyloid hypothesis and other, evolving hypotheses. We postulate that at least some patients develop AD due to autoimmune reactions between autoantibodies present in cerebral spinal fluid (CSF) against brain specific proteins. Our preliminary studies have clearly shown that some patients with Alzheimer’s disease possess either autoantibodies or autoimmune complexes in cerebral spinal fluid. By using state-of-the-art mass spectrometry we will identify such autoantibodies or immune complexes in a discovery phase, using a highly sensitive and specific assay that we recently developed. Once we identify candidate molecules in cerebral spinal fluid we will collaborate with a company, MesoScale Diagnostics, to develop targeted assays for about10 autoantibodies/immune complexes that can be assessed first in cerebral spinal fluid and later in serum. In association with an excellent biobank in Barcelona Spain (collaborator Dr. Morato) we will obtain high quality samples with clinical annotations from patients without Alzheimer disease, with mild moderate and sever Alzheimer disease and patients who have progressive or non-progressive disease. By using these valuable samples we will do the discovery experiments the first year followed by targeted assay development in the second year. Once we complete these objectives we intend to mound an extensive validation process to identify a group of autoantigens/immune complexes that can be used for differential diagnosis and monitoring of AD disease progression. We believe that our discovered biomarkers will be fundamental in clinical trials which are testing new agents which may be able to slow down or halt the disease at an early stage.