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

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $506,404

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Teich, Andrew, Franklin
Project Summary
The goal of this 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 this project, we will have a list of FDA-approved compounds that rescue synaptic MR dysfunction. Although
this is the primary endpoint of this project, we will also generate the following secondary deliverables; 1) A rat
neuronal interactome, which predicts a regulon for every transcriptional regulator in rat neurons, 2) A human
iPSC neuronal interactome, which predicts a regulon for every transcriptional regulator in human iPSC
neurons, and 3) A list of all transcriptional regulators affected by a library of FDA-approved compounds. These
additional deliverables will be usable for drug discovery of other neurologic diseases.
OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10165445
- **Project number:** 5R01AG059854-04
- **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:** $506,404
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165445

## Citation

> US National Institutes of Health, RePORTER application 10165445, A Translational Bioinformatics Approach to Rescuing Synaptic and Neurophysiologic Dysfunction in Alzheimer's Disease (5R01AG059854-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165445. Licensed CC0.

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