# Longitudinal in vivo imaging of synaptic pathologies of Alzheimer's disease

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $450,313

## Abstract

The synapse is the fundamental unit of the nervous system, enabling communication between brain cells and
providing a substrate for experience-dependent plasticity to drive adaptive behaviors. Altering the strength of
synapses between specific cells or neuronal ensembles is thought to underlie higher brain functions such as
learning and memory, whereas synaptic degradation is observed in many neurological pathologies, such as
Alzheimer's disease (AD) and related dementias. Despite the clear significance of synaptic communication, the
relationship between impaired synaptic function, progression of AD symptoms, and cognitive decline remains
unclear. However, recent breakthroughs in molecular microscopy enable direct imaging of the progression of
pathological synaptic deficits in mouse models of Alzheimer's disease. Our approach is to fluorescently tag
synaptic proteins and AD markers to track them throughout disease progression using in vivo two-photon
microscopy. By imaging large populations of synapses comprising entire cortical and hippocampal circuits, we
strive to gain a detailed understanding of how molecular pathologies affect synaptic physiology and ultimately
give rise to cognitive decline. This approach will yield a detailed time course of the progression of synaptic and
cognitive Alzheimer's pathologies that may reveal effective treatment windows and novel avenues for therapeutic
interventions for human disease.

## Key facts

- **NIH application ID:** 9895142
- **Project number:** 1R21AG063193-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Austin Robert Graves
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,313
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895142

## Citation

> US National Institutes of Health, RePORTER application 9895142, Longitudinal in vivo imaging of synaptic pathologies of Alzheimer's disease (1R21AG063193-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9895142. Licensed CC0.

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