# Selective targeting and treatment of plaque associated microglia in a mouse model of Alzheimer’s Disease

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $42,683

## Abstract

Project Summary
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder which is the most common cause of
severe dementia in elderly populations. Currently, there are no approved therapies which combat the
mechanisms behind AD, highlighting the need to develop more, effective treatments. AD is classically
characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), and brain-wide neuroinflammation. To
successfully create therapies treating AD, the mechanisms behind these pathological hallmarks must be better
understood. Recently, genome wide association studies (GWAS) have implicated many myeloid genes in the
modulation of AD. In the central nervous system, microglia are the primary resident myeloid cells, thus,
suggesting microglia are involved in AD. What is currently unknown, however, is whether microglial involvement
in AD is helpful or harmful. Microglial ablation studies and global microglial gene knockout studies show
conflicting results, possibly because these studies either globally alter gene transcription, or target all microglia
when multiple subsets of microglia exist in AD. To date, it has not been possible to selectively target these
discrete microglial populations to determine their relative roles and functions. To that end, we have developed
two approaches to selectively target and modulate plaque associated microglia while leaving non-plaque
associated microglia unaffected. Thus, I propose to 1) Determine the contribution of plaque associated microglia
to the pathogenesis of AD through a novel, inducible destabilized cre-lox mouse line targeting the gene
responsible for the microglial response to Aβ plaques, TREM2, and 2) Show proof of principle in being able to
pharmacologically alter the morphological and transcriptional profile of plaque associated microglia through
systemic administration of polyamidoamine hydroxyl dendrimers. Collectively, this proposal will elucidate the role
of plaque associated microglia in AD and showcase a potential therapeutic treatment for these cells, leading to
a clearer understanding of the role of microglia in AD outcomes.

## Key facts

- **NIH application ID:** 10620642
- **Project number:** 5F31AG072852-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Caden Michael Henningfield
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,683
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620642

## Citation

> US National Institutes of Health, RePORTER application 10620642, Selective targeting and treatment of plaque associated microglia in a mouse model of Alzheimer’s Disease (5F31AG072852-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10620642. Licensed CC0.

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