# A Translational Bioinformatics Approach to Rescuing Synaptic and Neurophysiologic Dysfunction in Alzheimer's Disease

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $404,508

## Abstract

Project Summary
The goal of our funded proposal is to identify FDA approved compounds that will rescue synaptic dysfunction
in Alzheimer's Disease (AD). This goal is motivated by the observation that one of the earliest events in AD is
synaptic dysfunction. In microscopic post-mortem studies, synaptic loss correlates strongly with pre-mortem
cognitive status, and serves as a better predictor of pre-mortem cognitive status than either plaque or tangle
pathology. Faced with this evidence, multiple groups have proposed that synaptic dysfunction is central to the
pathophysiology of AD. Our laboratory has previously utilized novel datamining techniques on RNA expression
data to identify master regulators of synaptic and neurophysiologic dysfunction in AD. This computational effort
has identified transcriptional regulators whose dysfunction in AD is predicted to cause impairment in
expression of synaptic genes (we refer to these transcriptional regulators as “synaptic master regulators,” or
synaptic MRs). Using similar techniques, we propose to screen a library of FDA-approved compounds for their
ability to support synaptic function in AD by appropriately modifying disease-relevant synaptic MRs. At the end
of our funded proposal, we will have a list of FDA-approved compounds that rescue synaptic MR dysfunction.
The goal of this supplement is to expand our drug screen to include compounds from a library of bioactive
compounds, which will screen for a wider range of therapeutic targets than is typically found in an FDA-
approved compound library. In addition, we will incorporate a fluorescent screening method to better image
neurite morphology in our neurons, which will be additive information that will help us eliminate compounds
that that negatively affect neurite integrity, complexity, and length. In summary, this supplement will allow us to
screen a wider range of compounds and will support gathering additional morphological information during our
screen, both of which will enhance the impact of our drug screen.

## Key facts

- **NIH application ID:** 10320653
- **Project number:** 3R01AG059854-04S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Andrew Franklin Teich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,508
- **Award type:** 3
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320653

## Citation

> US National Institutes of Health, RePORTER application 10320653, A Translational Bioinformatics Approach to Rescuing Synaptic and Neurophysiologic Dysfunction in Alzheimer's Disease (3R01AG059854-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320653. Licensed CC0.

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