PIs: Bradshaw, Elizabeth M., Ph.D. and Wassim Elyaman, Ph.D. Title: Microglia antigen presentation in the CNS of Alzheimer's disease Project Summary/Abstract Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive decline and dementia. Genome-wide association studies have identified novel AD susceptibility loci. Interestingly the associated genes at several of these loci implicate the immune system in late-onset AD (LOAD), specifically the innate immune system, including the human leukocyte antigen (HLA) region. The finding of the HLA region being genetically associated with LOAD further emphasizes the question of how microglia, the antigen-presenting cells of the central nervous system (CNS), interact with infiltrating T cells, which have been observed in the hippocampus of AD patients, and specifically what antigens are being presented. In parallel, the pathogen hypothesis has garnered more support for a possible pathogenic etiology of AD. We propose to leverage our understanding of the immune system combined with cutting-edge technology and access to AD patient blood and brain autopsies to determine if these neuroinvasive pathogens are neurovirulent in AD. For this application, we propose a multifaceted approach to: 1) identify the peptides being presented by the MHC of microglia in the AD brain in regions of high T cell infiltration and areas of low T cell infiltration; 2) examine the antigen reactivity and phenotype of T cells infiltrating the hippocampus in AD, and 3) determine how microglia function as antigen-presenting cells of pathogens to infiltrating T cells.

Public Health Relevance

PIs: Bradshaw, Elizabeth M., Ph.D. and Wassim Elyaman, Ph.D. Title: Microglia antigen presentation in the CNS of Alzheimer's disease Project Narrative Relevance to public health. This project is of direct relevance to Alzheimer's disease, as we are studying isolated immune populations from the CNS of individuals with Alzheimer's disease. We will be examining the phenotype, antigens being presented and antigen reactivity of individual single-immune cells. We will be examining the interaction of the pathogen hypothesis and the CNS immune cells in the human system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG067581-01
Application #
9976128
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mackiewicz, Miroslaw
Project Start
2020-05-15
Project End
2025-01-31
Budget Start
2020-05-15
Budget End
2021-01-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032