# Cell-type-specific and high-resolution profiling of postsynaptic proteomes altered in Alzheimer's disease model mice

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2020 · $423,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia with progressive loss of memory and cognitive
functions. In several AD model mice, the deficits in memory and cognitive functions are highly correlated with an
impairment in basal synaptic transmission and synaptic plasticity. Intriguingly, many of the AD model mice show
significant deficits in synaptic transmission and plasticity before the development of b-amyloid deposits, which is
a typical hallmark of AD pathology. Thus, synaptic dysfunction is a potentially important component of AD
pathogenesis. However, to understand the synaptic dysfunction in AD at molecular levels, we face a significant
obstacle, which is heterogeneity at multiple levels, due to neuronal heterogeneity and synaptic history (synaptic
plasticity). There is, therefore, a critical need to develop a biochemical method that can analyze synaptic
molecular constituents in a spatiotemporal manner to understand in substance the synaptic molecular alterations
involved in AD.
Here, the overall objective in this application is the development of systems-type biochemical methods that
enable cell-type-specific and high-resolution profiling of postsynaptic proteomes. The rationale for this project is
that these method developments are likely to advance the isolation of molecularly homogeneous postsynaptic
proteomes, which will ultimately provide more substantive maps of synaptic protein changes that contribute to
the synaptic dysfunction seen in AD.
To attain the overall objectives, the following two specific aims will be pursued: 1) Develop cell-type-specific
profiling methods of postsynaptic proteomes using Cre recombinase-dependent strategies; and 2) Develop high-
resolution profiling methods to identify sub-synaptic proteomes. This innovation in postsynaptic proteomics is
expected to allow us to isolate postsynaptic proteomes from the defined population of synapses and sub-synaptic
domains in AD model mice. More substantive profiles of synaptic molecular alterations in AD model mice will
provide a significant advance in the understanding of synaptic dysfunction in AD at molecular levels and new
opportunities for discovering therapeutic targets of AD.

## Key facts

- **NIH application ID:** 10045381
- **Project number:** 1R21AG068423-01
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Joongkyu Park
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,500
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045381

## Citation

> US National Institutes of Health, RePORTER application 10045381, Cell-type-specific and high-resolution profiling of postsynaptic proteomes altered in Alzheimer's disease model mice (1R21AG068423-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10045381. Licensed CC0.

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