# Phospholipase D1 Mediated Early Events Affecting Synaptic Dysfunction in Alzheimer's Disease and Related Dementia

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $395,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite significant research advances in the past two decades, Alzheimer’s disease (AD) remains the sixth
leading cause of death that cannot be prevented, cured or even slowed. Attention has shifted towards under-
standing early synaptic events in AD and related dementia (ADRD), resulting in memory deficits. However, the
mechanism recruited and leading to synapse dysfunction associated memory deficits remains elusive thus im-
peding successful therapeutic intervention. Bridging this critical gap in our current knowledge is the goal of this
proposal. We present compelling preliminary results that support our hypothesis that inducible phospholipase D
(PLD1) overexpression and the resulting aberrant signaling contributes to the progressive detrimental impact on
synapses and subsequent cognitive deficits. We will test our central hypothesis by pursuing the following specific
aims: (I) testing how elevated synaptic PLD1 levels/signaling contributes to synaptic dysfunction and memory
deficits in ADRD; (II) evaluating the functional contribution of elevated PLD1 in preclinical mouse models and
studying partners contributing to ADRD-like synaptic dysfunction and memory deficits. The present project is
highly significant because the proposed studies will establish elevated PLD1 and the associated signaling part-
ners as key players in promoting vulnerability causing progressive synaptic dysfunction and underlying cognitive
deficits. The successful completion of the aims will provide insight into the involved molecular mechanisms and
therapeutic possibilities using well-tolerated small molecule PLD1 inhibitor in preventing memory deficits asso-
ciated with ADRD progression. The proposed project will improve our scientific understanding of how synaptic
dysfunction is mediated by elevated PLD1 and interacting signaling partners in contributing to synaptic vulnera-
bility.

## Key facts

- **NIH application ID:** 9974025
- **Project number:** 1R01AG063945-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** BALAJI KRISHNAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974025

## Citation

> US National Institutes of Health, RePORTER application 9974025, Phospholipase D1 Mediated Early Events Affecting Synaptic Dysfunction in Alzheimer's Disease and Related Dementia (1R01AG063945-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974025. Licensed CC0.

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