# Locus Coeruleus Biomarker Development for Early Detection of Alzheimers Disease in Humans

> **NIH NIH R03** · BRANDEIS UNIVERSITY · 2021 · $162,500

## Abstract

Project Summary
The advent of neuroimaging methods for measuring locus coeruleus (LC) structural
integrity has generated intense interest from scientific fields focused on Alzheimer’s
disease (AD), psychiatric disorders, as well as basic cognitive neuroscience. The LC is
the brain’s primary generator of the neuromodulator norepinephrine (NE) and is one of
the first brain regions to accumulate hyperphosphorylated tau protein, a hallmark
pathological agent in AD. The ability to use magnetic resonance (MR) imaging to assess
LC integrity opens up exciting possibilities for earliest detection of disease acceleration,
and may also provide an MR measure that captures information about individual
differences in neurochemical function. The ability to study neurochemical systems in vivo
in humans is limited, with imaging approaches using radioactive tracers being the most
established (e.g. positron emission tomography (PET)). However, due to the burden to
subjects, as well as the infrastructural challenges, PET imaging is not a tool many
researchers use despite the central role neuromodulatory systems like NE play in basic
cognition and disease. We will take initial steps towards testing the validity of LC MR
measures for predicting NE function by examining the correspondence between a
neuromelanin-sensitive MR measure of LC integrity and a PET measure of
catecholamine (norepinephrine/dopamine) synthesis capacity ([18F]Fluoro-l-m-tyrosine
(FMT)) within subject in healthy young and older adults (Aim 1). Accumulating evidence
in healthy aging, AD, and Parkinson’s disease suggests the catecholamine system
responds to injury and shows compensatory capacity. Next, we will test the hypothesis
that with advancing age, catecholamine synthesis goes up (Aim 2). Finally, to test the
utility of LC neuroimaging measures as forecasters of the advancement of tau pathology,
we will explore whether neuromelanin-sensitive MR and [18F]FMT predict the
accumulation of tau in the medial temporal lobe using tau-sensitive [18F]flortaucipir
imaging (Aim 3). Together, this research takes critical steps in establishing MR
approaches as sensitive to neurochemical function, examines intriguing mechanisms of
neurochemical compensation, and provides empirical testing of models of pathological
spread in AD.

## Key facts

- **NIH application ID:** 10194679
- **Project number:** 1R03AG072328-01
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Anne Shively Berry
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194679

## Citation

> US National Institutes of Health, RePORTER application 10194679, Locus Coeruleus Biomarker Development for Early Detection of Alzheimers Disease in Humans (1R03AG072328-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194679. Licensed CC0.

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