# Defining lipid droplet homeostasis in Alzheimer's disease and aging with high molecular specificity using mass spectrometry imaging and isomer resolved lipidomics

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $562,005

## Abstract

SUMMARY
Loss of healthspan - declining health and function as we age – impacts nearly every living organism and is a
pronounced feature of Alzheimer’s disease and related dementias (ADRD), affecting nearly 6 million people in
the United States. Lipids are poorly understood central components of aging, having roles in healthy aging and
diseases of aging. The gap in lipid knowledge begins with a missing definition of ‘normal’ and extends to a lack
of understanding surrounding lipid fluctuations throughout life. Lipid homeostasis is an important component of
the healthy brain and both aging and multiple diseases are associated with alterations in lipid populations and
lipid droplet (LD) volume and count. Dysregulated lipid homeostasis is linked to inflammation, diabetes, forms
of liver failure, Gaucher disease, Parkinson’s disease, ADRD, and untold more pathologies. The failure to
understand lipids in health and disease can be explained by a lack of adequate tools to study lipids. With the
wide adoption of mass spectrometry tools, we recently entered the lipidomic era in which lipids can be
characterized in fine structural detail across a range of lipid classes with spatial sensitivity and relative or
absolute quantity. Spatial lipidomics using multimodal mass spectrometry imaging (MSI) produces regio-, cell-,
and organelle-specific lipid maps and reveals changes in tissue sections even when traditional, extracted
lipidomic studies fail to show changes. While progress has been made in spatial mapping of brain lipids in
aging and AD, these studies were limited by scope (lacking total lipid coverage, spatial resolution, and
structural specificity). Here, we will use leading edge high specificity and resolution spatial lipidomics to
describe the most thorough spatial lipid survey of aging brains possible, to date, using a combinatorial
approach. We will produce characteristic lipid fingerprints based on age, sex, disease state, and brain region.
These lipid fingerprints will be supported with phenotypic data and spatial transcriptomic data. These end result
will be an important resource for the aging and lipid research communities and will lead to new, translational
therapeutic approaches.

## Key facts

- **NIH application ID:** 10841656
- **Project number:** 5R01AG081436-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Alison J Scott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $562,005
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841656

## Citation

> US National Institutes of Health, RePORTER application 10841656, Defining lipid droplet homeostasis in Alzheimer's disease and aging with high molecular specificity using mass spectrometry imaging and isomer resolved lipidomics (5R01AG081436-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10841656. Licensed CC0.

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