Serum TCA cycle metabolites in Lewy bodies dementia and Alzheimer's disease: Network analysis and cognitive prognosis.

Autor: Jaramillo-Jimenez A; Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, School of Medicine, Medellín, Colombia; Semillero de Investigación SINAPSIS, Universidad de Antioquia, School of Medicine, Medellín, Colombia; Semillero de Investigación NeuroCo, Universidad de Antioquia, School of Medicine & School of Engenieering, Medellín, Colombia. Electronic address: alberto.jaramilloj@udea.edu.co., Giil LM; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway., Borda MG; Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana, Bogotá, Colombia., Tovar-Rios DA; Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; Universidad Del Valle, Grupo de Investigación en Estadística Aplicada - INFERIR, Faculty of Engineering, Santiago De Cali, Colombia; Universidad Del Valle, Prevención y Control de la Enfermedad Crónica - PRECEC, Faculty of Health, Santiago De Cali, Colombia., Kristiansen KA; Department of Biotechnology and Food Science, Norwegian University of Science and Technology, Trondheim, Norway., Bruheim P; Department of Biotechnology and Food Science, Norwegian University of Science and Technology, Trondheim, Norway., Aarsland D; Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK., Barreto GE; Department of Biological Sciences, University of Limerick, Limerick, Ireland., Berge RK; The Lipid Research Group, Department of Clinical Science, University of Bergen, Bergen, Norway.
Jazyk: angličtina
Zdroj: Mitochondrion [Mitochondrion] 2023 Jul; Vol. 71, pp. 17-25. Date of Electronic Publication: 2023 May 10.
DOI: 10.1016/j.mito.2023.05.002
Abstrakt: Abnormalities in the Tri-Carboxylic-Acid (TCA) cycle have been documented in dementia. Through network analysis, TCA cycle metabolites could indirectly reflect known dementia-related abnormalities in biochemical pathways, and key metabolites might be associated with prognosis. This study analyzed TCA cycle metabolites as predictors of cognitive decline in a mild dementia cohort and explored potential interactions with the diagnosis of Lewy Body Dementia (LBD) or Alzheimer's Disease (AD) and APOE-ε4 genotype. We included 145 mild dementia patients (LBD = 59; AD = 86). Serum TCA cycle metabolites were analyzed at baseline, and partial correlation networks were conducted. Cognitive performance was measured annually over 5-years with the Mini-mental State Examination. Longitudinal mixed-effects Tobit models evaluated each baseline metabolite as a predictor of 5-years cognitive decline. APOE-ε4 and diagnosis interactions were explored. Results showed comparable metabolite concentrations in LBD and AD. Multiple testing corrected networks showed larger coefficients for a negative correlation between pyruvate - succinate and positive correlations between fumarate - malate and citrate - Isocitrate in both LBD and AD. In the total sample, adjusted mixed models showed significant associations between baseline citrate concentration and longitudinal MMSE scores. In APOE-ε4 carriers, baseline isocitrate predicted MMSE scores. We conclude that, in mild dementia, serum citrate concentrations could be associated with subsequent cognitive decline, as well as isocitrate concentrations in APOE-ε4 carriers. Downregulation of enzymatic activity in the first half of the TCA cycle (decarboxylating dehydrogenases), with upregulation in the latter half (dehydrogenases only), might be indirectly reflected in serum TCA cycle metabolites' networks.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.)
Databáze: MEDLINE
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