title: Lymphocytic mitochondrial aconitase activity is reduced in Alzheimer's disease and mild cognitive impairment.
abstract: BACKGROUND
  Specific mechanisms behind the role of oxidative/nitrosative stress and mitochondrial dysfunction in Alzheimer's disease (AD) pathogenesis remain elusive. Mitochondrial aconitase (ACO2) is a Krebs cycle enzyme sensitive to free radical-mediated damage.
  
  
  OBJECTIVE
  We assessed activity and expression of ACO2 extracted from blood lymphocytes of subjects with AD, mild cognitive impairment (MCI), older adults with normal cognition (OCN, age ≥65 years), and younger adults with normal cognition (YCN, age <65 years). Plasma levels and activities of antioxidants were also measured.
  
  
  METHODS
  Blood samples were collected from 28 subjects with AD, 22 with MCI, 21 OCN, and 19 YCN. ACO2 activity was evaluated in a subsample before and after in vitro exposure to free radicals.
  
  
  RESULTS
  ACO2 activity was significantly lower in AD and MCI cases than controls: ACO2 median activity was 0.64 ± 0.21 U/mg protein for AD, 0.93 ± 0.28 U/mg protein for MCI, 1.17 ± 0.78 U/mg protein for OCN subjects, and 1.23 ± 0.43 U/mg protein for YCN individuals. In subjects with AD and MCI, ACO2 expression was lower than OCN subjects, and ACO2 activity correlated with vitamin E plasma levels (rho: 0.64, p < 0.001) and Mini-Mental State Examination total score (rho: 0.82, p < 0.001). Furthermore, free radicals exposure reduced ACO2 activity more in individuals with AD than in OCN subjects.
  
  
  CONCLUSIONS
  Our results suggest that ACO2 activity is reduced in peripheral lymphocytes of subjects with AD and MCI and correlates with antioxidant protection. Further studies are warranted to verify the role of ACO2 in AD pathogenesis and its importance as a marker of AD progression.
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy Aging Research Center, Karolinska Institutet-Stockholm University, Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mangialasche
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Baglioni
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cecchetti
authors.affiliation: Aging Research Center, Karolinska Institutet-Stockholm University, Stockholm, Sweden.
authors.forename: Miia
authors.initials: M
authors.lastname: Kivipelto
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Carmelinda
authors.initials: C
authors.lastname: Ruggiero
authors.affiliation: Department of Experimental Medicine - Section of Terni, University of Perugia, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Piobbico
authors.affiliation: Department of Central Nervous System Research, Boehringer-Ingelheim Pharma GmbH & Co, Biberach an der Riss, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kussmaul
authors.affiliation: Section of Neurology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Monastero
authors.affiliation: Department of Experimental Medicine - Section of Terni, University of Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Brancorsini
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
mesh_terms: D000154:Aconitate Hydratase / Q000097:blood*; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D060825:Cognitive Dysfunction / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008609:Mental Status Schedule; D008928:Mitochondria / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014810:Vitamin E / Q000097:blood
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D012333:RNA, Messenger; D014810:Vitamin E; C476079:ACO2 protein, human; D000154:Aconitate Hydratase
keywords: Aconitase (aconitate hydratase); Alzheimer disease; antioxidants; free radicals; lymphocyte; mild cognitive impairment; mitochondria; oxidative stress; reactive nitrogen species; reactive oxygen species