# Early anatomic markers and genetic risk factors for frontotemporal degeneration in amyotrophic lateral sclerosis

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $19,150

## Abstract

Project Summary
My long-term career goal is to become an independent translational neuroscientist with expertise in dementia
associated with neurodegenerative disease. This proposal is the first step in attaining this goal by combining a
comprehensive training plan with an innovative program of research to investigate early anatomic markers and
genetic risk factors for the progression of amyotrophic lateral sclerosis (ALS) to include frontotemporal
degeneration (ALS-FTD). An estimated 50% of ALS patients develop impairments in executive function,
personal and social behavior, and receptive and expressive language indicative of frontal and temporal lobe
neurodegeneration, and 10% of these individuals develop dementing impairments consistent with ALS-FTD.
ALS is a fatal neuromuscular disease, and ALS-FTD is consistently associated with significantly reduced time
of survival. End-stages of ALS implicate eventual frontal and temporal lobe disease, and causal pathogenic
mutations linking ALS and FTD have been identified; however, early indicators of ALS-FTD in patients with
sporadic (i.e. non-mutation) forms of disease are lacking. To identify early markers and risk factors for the
progression of ALS to ALS-FTD, I employ a series of advanced bioinformatics analyses of multimodal
neuroimaging, clinical, and genetic data from a large, well-characterized ALS patient cohort. I propose two
Aims: Aim 1) Identify early anatomic markers for progression from ALS to ALS-FTD by relating early, whole-
brain structural magnetic resonance imaging (sMRI) to decline on targeted assessments of cognition and
behavior, and Aim 2) Evaluate genetic risk factors for ALS-FTD in patients with sporadic disease by
investigating the neuroanatomic and neuropsychological profiles associated with risk alleles at 18 common
single nucleotide polymorphisms (SNPs) associated with ALS and FTD. I hypothesize that early frontal and
temporal neurodegeneration will serve as a sensitive in vivo marker for the progression from ALS to ALS-FTD,
and further hypothesize that this will by modified by SNPs that selectively confer risk for frontal and temporal
lobe neurodegeneration. My proposed research is innovative in several ways: 1) I focus on the identification of
early in vivo markers and risk factors for ALS-FTD, 2) I study patients with sporadic forms of disease, which
accounts for 90-95% of ALS, 3) I investigate complex, multivariate relationships between regional
neurodegeneration, genotype, and clinical symptoms in a comprehensive, network-based approach to the
study of dementia, and 4) I take a unique clinical neuroscience approach by recruiting patients from specialized
ALS and cognitive neurology clinics to minimize attainment bias. The knowledge gained from this project can
be used to define patient endophenotypes, design and stratify clinical trials, and identify therapeutic targets,
and also can be used in clinical settings to contribute to early identification, prognostication, a...

## Key facts

- **NIH application ID:** 9838277
- **Project number:** 5F31NS106754-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Katerina Placek
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $19,150
- **Award type:** 5
- **Project period:** 2018-02-01 → 2020-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838277

## Citation

> US National Institutes of Health, RePORTER application 9838277, Early anatomic markers and genetic risk factors for frontotemporal degeneration in amyotrophic lateral sclerosis (5F31NS106754-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838277. Licensed CC0.

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