# Brain mitochondrial PET imaging and 31P-MR spectroscopy to dissect the role of mitochondrial dysfunction in bioenergetic dysregulation in Dementia with Lewy Bodies pathogenesis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $1,569,417

## Abstract

PROJECT SUMMARY
Bioenergetic dysfunction is likely an early, critical component of neuropathogenesis of the second-most common
neurodegenerative dementia, Dementia with Lewy Bodies (DLB). However, it has been difficult to elucidate the specific
patterns and mechanisms of bioenergetic dysfunction, such as mitochondrial respiratory dysfunction, glycolytic failure, or
failure of energy reserves in vivo in the neuropathogenesis of this disease. Elucidating the different mechanistic pathways
of metabolic dysfunction involved in DLB pathogenesis, and determining the temporal sequence and pattern of these
events, will be critical to developing targeted therapies. Capitalizing on our combined expertise and our advancements in
neuroimaging methodologies, we have the capacity to combine a new PET radioligand that quantifies brain mitochondrial
Complex I, with both fluorodeoxyglucose (FDG)-PET to assess glycolytic energy metabolism, and ultra-high field strength
7T 31P-MRS for assessment of ATP and other high-energy phosphate bioenergetic metabolites. Utilizing this multimodal
neuroimaging, along with extensive clinical characterization, we will determine mitochondrial respiratory and glycolytic
contribution to ATP dysregulation across the clinical spectrum via evaluation of control, at-risk, prodromal, and clinically
established DLB. We will address the following aims: 1) characterize specific mitochondrial respiratory chain dysfunction
in the brain as DLB pathogenesis progresses from at-risk to established disease; 2) dissect specific bioenergetic pathways
contributing to ATP dysregulation in DLB; 3) analyze the relationship between brain mitochondrial and bioenergetic
dysfunction and changes in cognitive function and peripheral measurements of bioenergetics; and 4) explore differences
in bioenergetic pathway dysfunction between DLB and Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10928781
- **Project number:** 5R01AG080565-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** HOWARD J AIZENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,569,417
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928781

## Citation

> US National Institutes of Health, RePORTER application 10928781, Brain mitochondrial PET imaging and 31P-MR spectroscopy to dissect the role of mitochondrial dysfunction in bioenergetic dysregulation in Dementia with Lewy Bodies pathogenesis (5R01AG080565-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10928781. Licensed CC0.

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