# Blood Triglycerides and Fatty Acids in Alzheimer's: Genetics and Neuroimaging

> **NIH NIH F30** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $42,306

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) constitutes a substantial societal and personal burden. Clinical trial failures
indicate the need for a better mechanistic understanding of this complex disease. Triglycerides, which are
measured in routine clinical check-ups, are a source of fatty acids (FAs). Our previous work has shown a
significant association between polyunsaturated triglycerides (PUTGs) and AD. Interestingly, these PUTGs
were found to carry omega-3 polyunsaturated fatty acids (n-3 FAs), which have shown to improve cognitive
function in aging populations. Many clinical trials have investigated n-3 FA supplementation in AD patients,
but have resulted in disappointment. The literature does suggest a genetic influence on patient response to
n-3 FA supplementation. APOE ε4 is a genetic risk factor for late-onset AD. In AD patients, APOE ε4
noncarriers experience improved cognitive function, while APOE ε4 carriers do not experience the same
benefit. Our goal is to investigate the association of PUTGs and n-3 FAs with cross-sectional and
longitudinal changes in AD biomarkers, and the genomic contribution of PUTGs and n-3 FAs to pathologic
AD mechanisms. To achieve this goal, we will use a hypothesis-driven, integrative approach that will
incorporate multi-omics (genomics, metabolomics, transcriptomics) and multi-modal biomarker (blood, CSF,
neuroimaging) data. We will use data from ADNI, WRAP, and AMP-AD cohorts. First, we show preliminary
results for an association between baseline n-3 FAs and “A/T/N/V” (amyloid, tau, neurodegeneration, and
microvascular disease burden) biomarkers at baseline. We will test if PUTGs and n-3 FAs at baseline predict
longitudinal changes in A/T/N/V biomarkers up to 8 years and conversion of mild cognitive impairment (MCI)
to AD after 36 months from baseline. “A/T/N/V” is based on the recently proposed NIA-Alzheimer’s
Association 2018 Research Framework using CSF and neuroimaging biomarkers (brain atrophy and white
matter hyperintensity volume (MRI) and brain glucose metabolism (FDG-PET)). Second, we will investigate
genetic mechanisms that may contribute to AD pathophysiology by focusing specifically on PUTG and n-3
FA pathway-related genes. Using publicly available databases, we have manually curated a candidate gene
list that is related to PUTG and n-3 FA pathways and found associations between serum PUTG levels and
gene candidates. We will determine if genetic variation in PUTG and n-3 FA related-pathways associate with
serum n-3 FAs and A/T/N/V biomarkers at baseline and predict longitudinal changes in A/T/N/V biomarkers.
Finally, we will determine if these gene candidates are differentially expressed in AD and if genetic variations
have significant effects on gene expression levels in blood and brain. Our study has strong potential to
provide insight into how serum levels of PUTGs and n-3 FAs are associated with AD and to yield novel
diagnostic and therapeutic targets based on genetic-validated m...

## Key facts

- **NIH application ID:** 9984797
- **Project number:** 5F30AG063449-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Megan M Bernath
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,306
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984797

## Citation

> US National Institutes of Health, RePORTER application 9984797, Blood Triglycerides and Fatty Acids in Alzheimer's: Genetics and Neuroimaging (5F30AG063449-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9984797. Licensed CC0.

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