# Blood Base Bioenergetic Profiling: A Novel Approach for Identifying Alzheimer's Disease Risk and Pathology

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $746,785

## Abstract

7. Project Summary/Abstract
 In Alzheimer's disease (AD), irreversible neurological damage takes place years before the onset of
clinical symptoms. Therefore, it is recognized that the development of AD dementia treatment and prevention
strategies relies on the early detection of presymptomatic pathology. Previous studies demonstrate that
mitochondrial dysfunction plays a key role in the pathophysiology of AD and precedes the formation of plaques
and tangles that are hallmarks of this disease. The premise of this study is based on the unique sensitivity of
the brain to systemic bioenergetic decline due to its exceptionally high metabolic demand. We hypothesize that
bioenergetic capacity is related to early AD pathology and that bioenergetic decline is associated with the long
term progression and severity of this disease. Recent work by our group and others demonstrate that blood-
based bioenergetic profiling, utilizing cellular respirometry, provides a reliable measure of systemic
mitochondrial function. The proposed study will determine whether blood cell bioenergetics is related to AD
risk, pathology, cognitive performance, and changes in these parameters over time. Our long term goal is to
develop a minimally invasive screening tool that can be used in a clinic/community setting to identify
candidates for more intensive diagnostic testing, such as CSF biomarker analysis and brain imaging.
 This project will be completed in an efficient and cost-effective manner by leveraging resources
provided by the NIA-funded Wake Forest Alzheimer' Disease Center Clinical Core (ADCCC). Participants in
the ADCCC represent a spectrum of AD risk and disease progression and are being extensively characterized
for AD pathologies at baseline and 3 year follow ups. Our preliminary data from ADCCC participants indicate
that bioenergetic capacity, measured in blood cells, is lower in participants with mild cognitive impairment.
Moreover, our data suggest that bioenergetic deficits are already apparent in cognitively normal participants at
high risk for AD. The aims of the proposed study are: 1) To determine bioenergetic profiles most strongly
associated with AD risk and reporters of AD pathology (cognitive performance, CSF Aβ42/tau, hippocampal
volume, brain amyloid, and cerebral glucose metabolism); 2) To determine the changes in bioenergetic profiles
related to the 3 year progression of cognitive decline and reporters of AD pathology; and, 3) To determine the
relationships of mitochondrial content and inflammation with bioenergetic capacity, and reporters of AD
pathology at baseline and at follow-up. A central goal of the proposed study is to determine the specific
bioenergetic parameters that are most closely associated with AD risk and pathology. Therefore, in addition to
convention analytical approaches, we will employ state of the art Machine Learning analyses to identify
individual parameters or multivariate signatures that are most closely associated with AD...

## Key facts

- **NIH application ID:** 10174646
- **Project number:** 5R01AG054523-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ANTHONY J MOLINA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $746,785
- **Award type:** 5
- **Project period:** 2017-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174646

## Citation

> US National Institutes of Health, RePORTER application 10174646, Blood Base Bioenergetic Profiling: A Novel Approach for Identifying Alzheimer's Disease Risk and Pathology (5R01AG054523-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174646. Licensed CC0.

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