Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer's disease.
blood
cognitive decline
fatty-acid oxidation (FAO)
mitochondria
oxidative phosphorylation (OXPHOS)
peripheral blood mononuclear cells (PBMCs)
platelets
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
26
05
2022
received:
12
01
2022
accepted:
01
06
2022
pmc-release:
01
04
2024
medline:
17
4
2023
pubmed:
24
7
2022
entrez:
23
7
2022
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Identifiants
pubmed: 35870133
doi: 10.1002/alz.12731
pmc: PMC9868193
mid: NIHMS1818192
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1466-1478Subventions
Organisme : NIA NIH HHS
ID : R01 AG054523
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061805
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM127261
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG057864
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG060897
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072947
Pays : United States
Informations de copyright
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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