# Project 2- Correlating microglial activation with blood brain barrier integrity and neurocognitive performance

> **NIH NIH P01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $630,309

## Abstract

Project: 2 Summary/Abstract
Project 2 continues our focus on brain imaging studies in human SLE to investigate mechanisms of cognitive
dysfunction in patients with this disorder. The proposed study leverages the information gained in the last
funding cycle: the presence of consistent elevations in resting metabolic activity (a proxy for local synaptic
function) in the hippocampus of SLE patients, which correlated with anti DNA receptor antibody (DNRAb) titers
and with performance on cognitive test battery. In the next funding cycle, we plan to use multimodal PET and
MRI imaging tools to determine the mechanistic basis for cognitive dysfunction in this disorder. New
experimental evidence from Project 1 implicates microglial (MG) activation in the hippocampal neurotoxic
response to DNRAb. We will therefore use [11C]-PBR28 PET to assess this phenomenon in SLE patients
compared to healthy volunteer subjects. To this end, radiotracer uptake will be quantified in the hippocampus
and other metabolically active SLE-related brain regions. Using a longitudinal design, we will evaluate regional
MG activation over a two-year period, and determine how these changes relate to concurrent assessments of
cognitive functioning, DNRAb titers, and resting metabolic activity measured in the same subjects. Likewise,
we will use a quantitative MRI approach to evaluate BBB permeability in the hippocampus and in the other
SLE-related brain regions. Changes in this measure will similarly be compared with concurrent serological and
cognitive assessments, as well as with the other imaging descriptors of the underlying disease process. The
broad applicability of this approach may be limited, however, by the invasiveness of some of the imaging
methods. To make these assessments more clinically accessible, we will lastly explore the use of newer non-
invasive imaging tools as alternative disease markers. In summary, the multimodal imaging approach in
Project 2 will provide objective metrics for the assessment of new treatment strategies for SLE-CI.

## Key facts

- **NIH application ID:** 10885145
- **Project number:** 5P01AI073693-15
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** MEGGAN MACKAY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $630,309
- **Award type:** 5
- **Project period:** 2008-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885145

## Citation

> US National Institutes of Health, RePORTER application 10885145, Project 2- Correlating microglial activation with blood brain barrier integrity and neurocognitive performance (5P01AI073693-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10885145. Licensed CC0.

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