Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer's disease.

Autor:	Mahapatra G; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Gao Z; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Bateman JR 3rd; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.; Department of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Lockhart SN; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Bergstrom J; Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, USA., DeWitt AR; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Piloso JE; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Kramer PA; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Gonzalez-Armenta JL; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Amick KA; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Casanova R; Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA., Craft S; Section on Gerontology and Geriatrics, Sticht Center for Healthy Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA., Molina AJA; Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, USA.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Apr; Vol. 19 (4), pp. 1466-1478. Date of Electronic Publication: 2022 Jul 23.
DOI:	10.1002/alz.12731
Abstrakt:	Introduction: Despite evidence for systemic mitochondrial dysfunction early in Alzheimer's disease (AD) pathogenesis, reliable approaches monitoring these key bioenergetic alterations are lacking. We used peripheral blood mononuclear cells (PBMCs) and platelets as reporters of mitochondrial function in the context of cognitive impairment and AD. Methods: Mitochondrial function was analyzed using complementary respirometric approaches in intact and permeabilized cells from older adults with normal cognition, mild cognitive impairment (MCI), and dementia due to probable AD. Clinical outcomes included measures of cognitive function and brain morphology. Results: PBMC and platelet bioenergetic parameters were lowest in dementia participants. MCI platelets exhibited higher maximal respiration than normocognitives. PBMC and platelet respiration positively associated with cognitive ability and hippocampal volume, and negatively associated with white matter hyperintensities. Discussion: Our findings indicate blood-based bioenergetic profiling can be used as a minimally invasive approach for measuring systemic bioenergetic differences associated with dementia, and may be used to monitor bioenergetic changes associated with AD risk and progression. Highlights: Peripheral cell bioenergetic alterations accompanied cognitive decline in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and related dementia (DEM). Peripheral blood mononuclear cells (PBMC) and platelet glucose-mediated respiration decreased in participants with dementia compared to normocognitive controls (NC). PBMC fatty-acid oxidation (FAO)-mediated respiration progressively declined in MCI and AD compared to NC participants, while platelet FAO-mediated respiration exhibited an inverse-Warburg effect in MCI compared to NC participants. Positive associations were observed between bioenergetics and Modified Preclinical Alzheimer's Cognitive Composite, and bioenergetics and hippocampal volume %, while a negative association was observed between bioenergetics and white matter hyperintensities. Systemic mitochondrial dysfunction is associated with cognitive decline. (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
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