# Project 3: Autophagy dysfunction and neuronal activity in FTD

> **NIH NIH U54** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $319,504

## Abstract

Project 3: Autophagy dysfunction and neuronal activity in FTD Ana Maria Cuervo
SUMMARY
This proposal investigates the interplay between pathogenic forms of tau and selective forms of autophagy in
the context of frontotemporal dementia (FTD). We will coordinate the activities of this project with those of
Project 1 and Project 2 to test our working hypothesis that tau-mediated toxicity in the autophagic pathways
underlie the basis for the altered tau proteostasis and functional alterations observed in FTD-affected neurons.
Project 3 will use cutting edge proteomics (MS Core) and genetics (CRISPR Core) in iPSC-derived neurons to
investigate: 1) effect of pathogenic intra- and extracellular tau in the activity of three different forms of selective
autophagy; 2) consequences of blockage of each of these forms of autophagy on neuronal activity and tau
uptake. Project 3 will also utilize postmortem frozen human brain tissue from controls and FTD-tau patients
(Human Core) to identify 3) changes in the properties of tau associated with autophagic compartments in
control and patient brains. Assisted by the CRISPR Core, we will modulate levels of differentially tau-
interacting proteins and address the effect of this intervention on autophagy and neuronal activity.
Integration of data (Data Core) generated by this project with that from the other two projects in the Center will
allow us to elucidate the contribution of tau toxicity on the autophagic system to the neuronal activity imbalance
observed in FTD.

## Key facts

- **NIH application ID:** 10011929
- **Project number:** 5U54NS100717-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ANA MARIA CUERVO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,504
- **Award type:** 5
- **Project period:** 2016-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011929

## Citation

> US National Institutes of Health, RePORTER application 10011929, Project 3: Autophagy dysfunction and neuronal activity in FTD (5U54NS100717-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10011929. Licensed CC0.

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