# Stress hormone, calcium spikes and synapse loss in Alzheimer’s disease

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $211,875

## Abstract

The goal of this proposal is to establish the link among stress, Ca2+ dysregulation and synapse loss in aging and
a mouse model of Alzheimer's disease (AD). AD is the most common cause of dementia in the elderly. Synapse
loss occurs many years before dementia and is the best correlate of cognitive impairment in AD patients. In the
APPPS1 mouse model of AD, we have recently found that a fraction of dendrites of pyramidal neurons exhibit
abnormal high-amplitude long-duration dendritic Ca2+ spikes, which result in synaptic depotentiation. We have
also found that the deletion of glucocorticoid receptors (GR) phosphorylation at brain-derived neurotrophic factor
(BDNF)-responding sites increases the amplitude and frequency of dendritic Ca2+ spikes. Based on these
findings, we propose to test the hypothesis that stress hormone glucocorticoids promote abnormal dendritic Ca2+
spikes and lead to synaptic dysfunction and loss while BDNF reduces these detrimental effects by affecting GR
phosphorylation and its signaling pathway. To alleviate the generation of abnormal dendritic Ca2+ spikes and
their detrimental consequences on synaptic plasticity, we will investigate the impact of reducing stress hormone
glucocorticoids or increasing BDNF activity by genetic or pharmacological manipulations in the AD mouse model.
The proposed experiments will determine the role of stress in the generation of abnormal dendritic Ca2+ spikes
and synapse loss in aging and AD pathogenesis. The proposed studies will also generate important new insights
into the therapeutic treatment of AD aiming at reducing stress, Ca2+ dysregulation and synapse loss.

## Key facts

- **NIH application ID:** 9867614
- **Project number:** 5R21AG061751-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** MOSES VICTOR CHAO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-02-15 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867614

## Citation

> US National Institutes of Health, RePORTER application 9867614, Stress hormone, calcium spikes and synapse loss in Alzheimer’s disease (5R21AG061751-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9867614. Licensed CC0.

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