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

Award Number: R01AG054523
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Blood Base Bioenergetic Profiling: A Novel Approach for Identifying Alzheimer's Disease Risk and Pathology - 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 risk and pathology. Completion of this project can impact the detection of presymptomatic AD, provide insights into mechanisms underlying bioenergetic decline associated with AD, and broadly advance translational bioenergetics research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	5	9/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	5	4/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	5	5/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $746,785 )
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	5	4/27/2021	NON-COMPETING CONTINUATION	$746,785
														Subtotal = $746,785

Issue Date FY: 2020 ( Subtotal = $752,198 )
2020	2020	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	4	5/29/2020	NON-COMPETING CONTINUATION	$752,198
														Subtotal = $752,198

Issue Date FY: 2019 ( Subtotal = $760,616 )
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3	8/5/2019	NON-COMPETING CONTINUATION	$760,616
														Subtotal = $760,616

Issue Date FY: 2018 ( Subtotal = $759,065 )
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	2	4/26/2018	NON-COMPETING CONTINUATION	$759,065
														Subtotal = $759,065

Issue Date FY: 2017 ( Subtotal = $766,314 )
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	1	6/28/2017	NEW	$766,314
														Subtotal = $766,314

Grand Total All Awards = $3,784,978

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

Award Number: R01AG054523

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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