# Project 3

> **NIH NIH P20** · CLEVELAND CLINIC FOUNDATION · 2021 · $238,533

## Abstract

SUMMARY/ABSTRACT 
 PROJECT R-3 
The Role of Inflammation in Ad-Related Network Dysfunction in Mice (Dr. Hyman) 
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory 
function. Much research has concentrated on the pathological hallmarks of AD, amyloid-beta (Aβ) plaque 
deposition, tau hyperphosphorylation, neurofibrillary tangle formation, and the progressive loss neurons and 
synapses. Recently, studies have shown that immune activation, in the form of neuroinflammation and 
associated microglial activation, may contribute to progression of the classic AD pathologies, but the role neural 
inflammation plays in memory impairments observed in AD patients is unknown. Memory formation and retrieval 
are the products of interconnected networks of brain structures including the hippocampus (HC) and anterior 
cingulate cortex (ACC). Work with transgenic animal models that develop AD pathologies (Aβ deposition or tau 
hyperphosphorylation) has revealed altered electrical activity in the HC prior to the development of mass 
amyloidosis or tauopathy. This type of altered network activity may explain the appearance of memory deficits 
early in AD progression. All of the different transgenic models show severe neuroinflammation, however, whether 
the network dysfunction is due to the immune response or the classic AD pathologies remains unknown. 
Investigating the impact of neuroinflammation on memory-linked network activity can help to identify future 
therapeutic targets and potential biomarkers. 
 Project 3 will investigate the effects of chronic or acute neuroinflammation on HC and ACC network 
activity. We will examine whether neuroinflammation affects different stages of memory processing (encoding, 
consolidation, retrieval) and whether the effects are localized to the HC or ACC or if they alter interactions 
between these areas. We plan to correlate our electrophysiological findings with markers of neuroinflammation 
to better understand how these factors work together in altering network activity. Next, we will examine whether 
increased neuroinflammation exacerbates the altered network activity observed in early stage pathology Aβ and 
tau transgenic models. If neuroinflammation leads to increased network dysfunction in the HC and ACC, these 
results support our overall hypothesis that NI itself is impairing memory network activity. These data will provide 
valuable information for a mechanism through which memory impairments appear in AD and AD transgenic 
animal models.

## Key facts

- **NIH application ID:** 10271799
- **Project number:** 2P20GM109025-06A1
- **Recipient organization:** CLEVELAND CLINIC FOUNDATION
- **Principal Investigator:** James M. Hyman
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,533
- **Award type:** 2
- **Project period:** 2015-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271799

## Citation

> US National Institutes of Health, RePORTER application 10271799, Project 3 (2P20GM109025-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10271799. Licensed CC0.

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