# Temporal, Spatial and Cellular Dynamics of Amyloid Plaque Deposition

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $2,261,484

## Abstract

Project Summary
Amyloid plaques are one of the canonical pathological hallmarks of Alzheimer's disease (AD).
The amyloid hypothesis is a standard model for amyloid Abeta pathogenesis that has driven
drug discovery for the past 25 years, giving rise to many clinical failures, including drugs that
make the treated patients cognitively worse than the placebo-treated controls. Aducanumab
(Aduhelm) is the first disease modifying treatment recently approved by the FDA on the basis of
its ability to facilitate the removal of amyloid plaques, indicating the importance of these
strictures. There are several different types of plaques and amyloid deposits known in AD,
including diffuse, “classical” “dense core”, neuritic plaques and cerebrovascular amyloid (CVA)
and intraneuronal amyloid deposits. While there is much that is known about amyloid plaque
morphology and composition in AD, less is known about mechanisms of plaque deposition, their
dynamics and interrelationships, the contributions of different cell types to their formation and
their significance for AD pathogenesis. We seek to investigate these critical aspects of amyloid
plaque deposition in a detailed and un unbiased fashion by labeling the proteome of specific cell
types with the non-canonical amino acid, azidonorleucine, and following the incorporation of
ANL-labeled proteins into amyloid deposits. The goal of this proposal is to determine the
temporal, spatial and cellular dynamics of amyloid deposition using cutting-edge biorthogonal
non-canonical amino acid tagging (BONCAT) technology and specific Cre driver mouse lines for
cell specific synthesis of clickable proteins, exploiting click chemistry for fluorescence
localization (FUNCAT), purification and enrichment and biochemical analysis. Our central
hypothesis is that different types of plaques are deposited by different mechanisms at different
times and locations by different populations neurons and that some of these types of plaques
may be mechanistically unrelated to the other types of amyloid and may be differentially
associated with pathogenesis and neuronal degeneration.

## Key facts

- **NIH application ID:** 10525630
- **Project number:** 1RF1AG079185-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Charles G. Glabe
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,261,484
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525630

## Citation

> US National Institutes of Health, RePORTER application 10525630, Temporal, Spatial and Cellular Dynamics of Amyloid Plaque Deposition (1RF1AG079185-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10525630. Licensed CC0.

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