# Assessing cell specific proteomes in the presence and absence of C5a complement signaling in Alzheimer's disease models

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $228,360

## Abstract

Project Summary.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of the elderly. The complement
cascade, a powerful effector mechanism of the innate immune system that can be directly activated by fibrillar
Aβ, is implicated as a player in this inflammatory scenario. In brain, expression of most complement components
increases during aging and further increases in AD patients and animal models of AD, consistent with a role for
complement immune activation in progression of the disease. Complement activation fragment C5a has been a
major focus, as inhibition of its proinflammatory receptor, C5aR1, leads to less activation of microglia and
astrocytes, preservation of neuronal complexity and reduction of cognitive loss in AD models. These critical
observations strongly suggest C5a binding to its receptor C5aR1 initiates cellular activation leading to changes
in protein expression in microglia and astrocytes, which result in pathological phenotypes and disease
progression. The primary goal of this proposal is to systemically understand alterations in cell-specific protein
expression that result from signaling via C5a-C5aR1 in the context of Alzheimer’s disease. Specifically, this will
extend our knowledge of induction of specific RNAs to production of the proteins, and the contribution of each
cell type to those functional proteins, that ultimately accelerate pathogenesis and neuronal dysfunction in
Alzheimer’s disease models.

## Key facts

- **NIH application ID:** 10046003
- **Project number:** 1R21AG068573-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Robert C Spitale
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,360
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046003

## Citation

> US National Institutes of Health, RePORTER application 10046003, Assessing cell specific proteomes in the presence and absence of C5a complement signaling in Alzheimer's disease models (1R21AG068573-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046003. Licensed CC0.

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