# Fatty acid trafficking in astrocytes: role of mitochondrial morphology and lipid droplet dynamics

> **NIH NIH R00** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $248,999

## Abstract

PROJECT SUMMARY/ABSTRACT: Fatty acid trafficking in astrocytes: role of mitochondrial
morphology and lipid droplet dynamics
 As the population of the United States ages, the burden of both dementia and obesity-related
disorders is increasing. There is mounting evidence that obesity, metabolic syndrome, and diabetes can
contribute to the progression of dementias such as Alzheimer's disease. Therefore, it is crucial to
understand the interplay between metabolism and neurodegeneration. A candidate protein linking
metabolism and AD is ApoE. ApoE is involved in the transport of lipids, including fatty acids (FAs) and
cholesterol, in the brain. Of all the identified genetic risk factors for developing late onset AD, a particular
version of the APOE gene called the APOE4 allele is the strongest predictor of risk. How the ApoE4 protein
contributes to the progression of AD is not understood. ApoE is not normally expressed in neurons, but is
expressed in astrocytes. Astrocytes are cells in the brain that supply neurons with many metabolic building
blocks, including FAs. The proposed study will use advanced microscopy techniques to investigate the
storage, metabolism, and trafficking of FAs within astrocytes, and between astrocytes and neurons. In Aim
1, the effect of ApoE on FA storage and metabolism in astrocytes will be examined. The effect of ApoE
expression in astrocytes on the transfer of FAs from astrocytes to neurons will also be tested, and the effect
of FA transfer from astrocytes to neurons on neuronal health and synaptogenesis will be determined. In Aim
2, the hypothesis that ApoE affects mitochondrial morphology and function will be tested. Mitochondria are
the cellular compartment responsible for metabolizing FAs. ApoE has been implicated in mitochondrial
dysfunction, but the mechanism is unclear. Lastly, in Aim 3 the hypothesis that ApoE affects the interaction
between lipid droplets and other cellular compartments will be investigated. Lipid droplets are the cellular
compartment responsible for storing fat. Thus, the exchange of FAs between lipid droplets and other cellular
compartments responsible for synthesizing and oxidizing FAs is likely to have an impact on FA trafficking
within astrocytes, and between astrocytes and neurons. Together, these studies will provide insight into the
links between metabolism and neurodegeneration. This could lead to new approaches for early intervention
to slow or prevent Alzheimer's disease, for example by targeting metabolic pathways that control the
storage or trafficking of FAs in astrocytes. Such interventions have the potential to dramatically improve the
quality of life of patients suffering from Alzheimer's disease and other dementias.

## Key facts

- **NIH application ID:** 9850179
- **Project number:** 5R00AG052570-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sarah Cohen
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2018-04-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850179

## Citation

> US National Institutes of Health, RePORTER application 9850179, Fatty acid trafficking in astrocytes: role of mitochondrial morphology and lipid droplet dynamics (5R00AG052570-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850179. Licensed CC0.

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