# Clinicopathologic correlates of cognitive impairment in amyotrophic lateral sclerosis and frontotemporal dementia spectrum disorders (ALS-FTD)

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $47,256

## Abstract

PROJECT SUMMARY
Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) is a neurodegenerative disorder with
clinical presentations ranging from progressive paralysis to cognitive impairment. FTD is the second most
common cause of dementia in people under the age of 65 and accounts for 25% of cases of dementia in
people over 65 years of age. Approximately 15% of ALS-FTD patients initially presenting with motor symptoms
also receive a diagnosis of dementia, but a majority of ALS-FTD patients demonstrate some level of cognitive
impairment over the course of disease. Identifying molecular pathways that contribute to the development of
cognitive deficits in ALS-FTD has thus far been limited by the quality of clinical information and postmortem
tissue preservation as well as available technologies. Our collaborators at the University of Edinburgh have
assembled a cohort of non-demented ALS-FTD patients with detailed cognitive profiling and high quality
postmortem tissue preservation for molecular studies. Novel highly multiplexed protein imaging and spatially
resolved transcriptomics methods have made it possible to quantify cell type composition and gene expression
in situ in postmortem tissue sections. These experimental advances have the potential to elucidate molecular
mechanisms that are associated with cognitive dysfunction in ALS-FTD.
 This proposal seeks to understand how TDP-43 pathology and local changes in the tissue
microenvironment contribute to cognitive impairment in patients with ALS-FTD. By integrating multiplexed
imaging and spatial transcriptomics data, I will quantify cell type proportions (Aim 1) and perturbations in gene
expression (Aim 2) proximal to TDP-43 pathology in postmortem tissues from this cohort of ALS-FTD patients
with detailed clinical and neuropathological characterization. By comparing these features in patients with and
without cognitive dysfunction, I will identify molecular pathways that may contribute to or protect against
cognitive impairment in ALS-FTD. This multimodal approach can be applied to study clinicopathologic
correlates of other proteinopathies.
 My fellowship proposal also outlines a rigorous training plan focused on developing the intellectual and
professional skills required for a successful career as a physician scientist: 1) designing rigorous, well-
controlled and well-powered studies, 2) effective science communication through oral presentations,
manuscript writing and grant writing, 3) cutting-edge experimental and computational genomics methods, 4)
mentorship of trainees and collaboration with scientists from other disciplines, and 5) placing research in a
clinical context. As a predoctoral trainee, I will benefit from the mentorship of Dr. Hemali Phatnani and Dr. Tom
Maniatis, the expertise of our neuropathology, engineering, and computational collaborators, and the
collaborative and supportive training environments at the New York Genome Center and the Columbia
University Irvi...

## Key facts

- **NIH application ID:** 10389064
- **Project number:** 1F30AG072766-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joana Petrescu
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,256
- **Award type:** 1
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389064

## Citation

> US National Institutes of Health, RePORTER application 10389064, Clinicopathologic correlates of cognitive impairment in amyotrophic lateral sclerosis and frontotemporal dementia spectrum disorders (ALS-FTD) (1F30AG072766-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389064. Licensed CC0.

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