# Calcium dysregulation and vulnerability of entorhinal cortex neurons in Alzheimer's disease

> **NIH NIH R56** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $698,240

## Abstract

ABSTRACT
The broad, long-term objective of this multi-PI grant application is to understand the role of calcium (Ca2+)
dysregulation as the mechanistic driver for synaptic loss between the lateral entorhinal cortex (LEC) and
hippocampus (HPC) in evolving Alzheimer’s disease (AD). While dysfunction of LEC-HPC circuit has been
implicated in the early stages of AD, the cause of this early, selective vulnerability of LEC neurons and
disruption of LEC-HPC connections remain unknown. In our studies we will test the hypothesis that
dysregulation of neuronal Ca2+ signaling plays a key role in LEC-HPC circuit dysfunction in early AD.
Specifically, in experiments with the APPKI mouse model of AD, we will investigate if normalization of
the activity of the Ca2+-dependent phosphatase calcineurin (CaN) rescues defects in LEC–HPC
communication in early AD. The peptidyl-prolyl isomerase Pin1 is one of the key targets of CaN in neurons.
Elevations in CaN inhibit Pin1, directly leading to synaptic and neuronal loss. In experiments with APPKI
mice, we will determine if restoration of Pin1 activity rescues defects in LEC–HPC communication in
early AD. We will use a combination of molecular, biochemical, imaging, electrophysiological, behavioral and
neuropathological techniques to address these specific aims. If successful, our studies will provide a
mechanistic rationale for the use of CaN inhibitors to treat early AD, potentially correcting early dysfunction of
the LEC-HPC circuit and slowing AD development.

## Key facts

- **NIH application ID:** 10459711
- **Project number:** 1R56AG071310-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Ilya B Bezprozvanny
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $698,240
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459711

## Citation

> US National Institutes of Health, RePORTER application 10459711, Calcium dysregulation and vulnerability of entorhinal cortex neurons in Alzheimer's disease (1R56AG071310-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10459711. Licensed CC0.

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