# Immune cell activation and associated blood brain barrier changes across different stages of Alzheimer's disease

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $779,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Age-related diseases, such as Alzheimer's disease (AD), are defining public health concerns of the 21st
century and are the leading cause of disability worldwide. A growing body of evidence notes that central
nervous system immune changes superimposed on ongoing chronic neurodegeneration may have a major
impact on disease progression in AD and other neurodegenerative conditions. The role of the peripheral
immune system in AD, including cellular elements of both the innate and adaptive immunity are still
enigmatic. In this proposal, we investigate immune cell identity and abundance in the periphery and
cerebrospinal fluid (CSF) at single cell resolution among preclinical-AD, MCI-AD, and AD-Dementia
stages and among normal aging controls. Furthermore, a novel aspect of this study will be to corroborate
the severity of blood brain barrier (BBB) changes associated with specific immune cell profiles noted in CSF
and the periphery across AD stages and its impact on longitudinal cognitive decline. Our overall goal is to
characterize immune cell identity and abundance in the periphery and the CNS at single cell resolution
across different AD clinical stages and in tandem, to clarify the peripheral anatomical context of immune
cell activation and the degree of BBB changes, with the goal of understanding the temporal course of
immune response in relation to initiation of clinical decline and subsequent phenotypic heterogeneity of AD
trajectories. Towards this, we will investigate immune cell phenotypes in the CSF and peripheral blood by a
powerful single-cell proteomic analysis technique, mass cytometry, and BBB changes will be delineated by
dynamic contrast-enhanced MRI techniques in the same subjects.
Data integrating peripheral and CSF adaptive and innate immune cell activation along with BBB changes
across different stages of AD will help develop a clear rationale for the use of these markers
in the AmyloidTau(Neurodegeneration) framework. Additionally, these insights will help future therapeutic
targeting of specific immune and BBB changes at the most effective clinical stage of disease. The results from
the study will also enable the identification of novel mechanisms that regulate immune cell homeostasis in the
periphery and the CNS, and the state of BBB, providing potential means to manipulate these immune cells
for therapeutic purposes in the future.

## Key facts

- **NIH application ID:** 10515907
- **Project number:** 1R01AG078763-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** JAGAN AYYAPPAN PILLAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $779,250
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10515907

## Citation

> US National Institutes of Health, RePORTER application 10515907, Immune cell activation and associated blood brain barrier changes across different stages of Alzheimer's disease (1R01AG078763-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10515907. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*