# Expanding insights into FTD disease mechanisms

> **NIH NIH R35** · MAYO CLINIC  JACKSONVILLE · 2021 · $963,625

## Abstract

ABSTRACT
Up to two thirds of hospitalized COVID-19 patients show neurologic signs and symptoms. For example, some
patients with COVID-19 experience cognitive changes (or brain fog) or suffer strokes and seizures. It is
hypothesized that COVID-19-induced brain inflammation and white matter damage underpin the neurological
manifestations experienced by patients with COVID-19. Since neuroinflammation and white matter damage are
also implicated in Alzheimer’s disease related dementias (ADRDs), COVID-19 may increase the risk of
developing an ADRD. Nevertheless, many questions remain answered, and the subacute and long-term
neurological effects of COVID-19 are unknown. We thus propose to undertake a comprehensive longitudinal
study of patients with COVID-19 requiring hospitalization. To identify patients at risk of long-term neurological
complications and warranting follow-up visits, levels of serum neurofilament light chain (NFL), a marker of neuron
injury, will be measured in hospital. We based this on our recent findings that ~53% of an initial cohort of 142
hospitalized patients with COVID-19 had elevated serum NFL, and that higher NFL concentrations correlated
with worse clinical outcomes, including the need for mechanical ventilation, intensive care unit admission, longer
lengths of hospitalization and poor functional outcomes. As such, NFL measurements provide an efficient means
to estimate the extent of neurological injury associated with the acute infection and pending systemic metabolic
disturbances. We will follow consenting patients 3 months, 1 year and 2 years after discharge, and examine
blood biomarkers of neuronal and astroglial injury, ADRD pathologies and neuroinflammation, imaging markers
of neuroinflammation and Aβ deposition, and cognitive outcomes. These data will allow us to determine whether
blood biomarker levels during hospitalization predict the emergence and severity of ADRD-related neurological
signs and symptoms. We will also extend our prior neuropathological studies in patients with COVID-19 and
ADRDs, and assess anoxic-ischemic cerebral white matter damage, neuroinflammation and microglial activation.

## Key facts

- **NIH application ID:** 10401522
- **Project number:** 3R35NS097273-05S1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** LEONARD PETRUCELLI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $963,625
- **Award type:** 3
- **Project period:** 2021-06-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401522

## Citation

> US National Institutes of Health, RePORTER application 10401522, Expanding insights into FTD disease mechanisms (3R35NS097273-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401522. Licensed CC0.

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