An estimated 5 million Americans suffer from Alzheimer?s disease (AD) which is a complex, multi-factorial disease of the brain. We observed that AD patients display a more robust expansion of innate cell populations in the cerebrospinal fluid than patients with the classic neuro-inflammatory disease, Multiple Sclerosis (MS)(35.0% vs 2.6%, AD:MS, p=0.002). Furthermore, AD patients display a decreased frequency of CD4+ T cells in the CSF compared to MS patients (37.8% vs 61.5%, AD:MS, p=0.01). These immune profile alterations in the CSF of AD patients was also observed in the blood. Thus, we hypothesize that expansion of innate immune cells and contraction of CD4+ T cells as observed in the CSF and periphery contributes to AD development by impacting antibody production against Abeta and Tau. To test this hypothesis, we will collect cerebrospinal fluid and peripheral blood from AD patients and age- matched HDs and analyze cellular and molecular aspects of the humoral immune compartment. The results of this study may support the expanded use of immune-stimulating therapies at an earlier stage of disease when they are most likely to be effective.

Public Health Relevance

LAY SUMMARY Alzheimer?s Disease has become one of the most intensely studied research areas of this decade. Our studies have revealed that patients with Alzheimer?s have a reduced population of a type of immune cell called a T cell. Our goal is to determine the impact of this T cell reduction on antibody production, which could be important in clearance of Abeta plaques in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS104509-02
Application #
9733360
Study Section
Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section (HAI)
Program Officer
Corriveau, Roderick A
Project Start
2018-07-01
Project End
2020-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Neurology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390