# Calcineurin activation and scaffolding in A Beta-induced synaptic dysfunction

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2021 · $66,390

## Abstract

Project Summary
Alzheimer’s disease (AD) is the most common form of dementia, with growing prevalence as the aging
population continues to grow. Pathologically, this neurodegenerative disease is characterized by amyloid-β
(Aβ) plaques and tau tangles. Acute application of Aβ has been shown to inhibit NMDA receptor (NMDAR)-
dependent long-term potentiation (LTP, a key form of neuronal plasticity critical for learning and memory), and
chronic Aβ exposure caused long-term depression (LTD) and elimination of excitatory synapses. Normal LTD
requires the protein phosphatase Calcineurin (CaN) and pharmacological inhibition of CaN prevents Aβ-
mediated LTP inhibition and synapse loss in rodent models. However, we not know where in the complex
organization and architecture of the nervous system CaN is acting to promote these deleterious impacts of Ab
on synaptic function. Here I will test the novel hypothesis that LTP inhibition, excitiatory synapse loss, and
impaired cognition associated with mouse models of AD are due to Aβ triggering aberrant postsynaptic CaN
activation in hippocampal pyramidal neurons. I will further test whether CaN that is specifically localized to
postsynaptic sites by the scaffolding protein AKAP79/150 is responsible for mediating these synaptotoxic
effects of Aβ at the molecular, cellular and behavioral levels in an effort to uncover potentially new therapeutic
targets.

## Key facts

- **NIH application ID:** 10312481
- **Project number:** 1F32AG071073-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Olga Prikhodko
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-08-11 → 2024-08-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312481

## Citation

> US National Institutes of Health, RePORTER application 10312481, Calcineurin activation and scaffolding in A Beta-induced synaptic dysfunction (1F32AG071073-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312481. Licensed CC0.

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