Online citations, reference lists, and bibliographies.
← Back to Search

Lymphocytic Mitochondrial Aconitase Activity Is Reduced In Alzheimer's Disease And Mild Cognitive Impairment.

F. Mangialasche, M. Baglioni, R. Cecchetti, M. Kivipelto, C. Ruggiero, D. Piobbico, L. Kussmaul, R. Monastero, S. Brancorsini, P. Mecocci
Published 2015 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
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. CONCLUSION 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.
This paper references
The assessment of anxiety states by rating.
M. Hamilton (1959)
"Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.
Gel electrophoresis of proteins: a practical approach
B. Hames (1981)
Analysis of covariance using the rank transformation.
W. Conover (1982)
A new clinical scale for the staging of dementia.
C. P. Hughes (1982)
Clinical diagnosis of Alzheimer's disease
G. Mckhann (1984)
Assays of glutathione peroxidase.
L. Flohé (1984)
Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version.
J. Sheikh (1986)
An internal standard method for the unattended high-performance liquid chromatographic analysis of ascorbic acid in blood components.
M. A. Kutnink (1987)
Structure of activated aconitase: formation of the [4Fe-4S] cluster in the crystal.
A. Robbins (1990)
[21] Automated assay of superoxide dismutase in blood
M. L’Abbé (1990)
A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples.
D. Nierenberg (1992)
Superoxide Radical and Iron Modulate Aconitase Activity in Mammalian Cells (*)
P. R. Gardner (1995)
Oxidative damage during aging targets mitochondrial aconitase.
L. Yan (1997)
Oxidative damage to DNA in lymphocytes from AD patients
P. Mecocci (1998)
Inactivation of aconitase and oxoglutarate dehydrogenase in skeletal muscle in vitro by superoxide anions and/or nitric oxide.
U. Andersson (1998)
Mild cognitive impairment: clinical characterization and outcome.
R. Petersen (1999)
Current concepts in mild cognitive impairment.
R. Petersen (2001)
Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism
D. Bota (2002)
Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.
P. Mecocci (2002)
Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease.
Mónika Mórocz (2002)
Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease
P. Rinaldi (2003)
Redox-dependent modulation of aconitase activity in intact mitochondria.
A. Bulteau (2003)
Proteomics: a new approach to investigate oxidative stress in Alzheimer's disease brain
D. Butterfield (2004)
Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment
B. Winblad (2004)
Plasma Antioxidant Status, Immunoglobulin G Oxidation and Lipid Peroxidation in Demented Patients: Relevance to Alzheimer Disease and Vascular Dementia
M. Polidori (2004)
Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses
E. Blalock (2004)
Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats.
G. Vatassery (2004)
Impairment of Brain Mitochondrial Oxidative Phosphorylation Accompanying Vitamin E Oxidation Induced by Iron or Reactive Nitrogen Species: A Selective Review
G. Vatassery (2004)
Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer's disease.
D. Praticò (2004)
Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications
P. Bubber (2005)
Role of mitochondria in toxic oxidative stress.
M. W. Fariss (2005)
Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
M. Lin (2006)
Redox proteomics identification of oxidatively modified proteins in Alzheimer's disease brain and in vivo and in vitro models of AD centered around Abeta(1-42).
R. Sultana (2006)
Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease.
V. Calabrese (2006)
Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice
C. Yarian (2006)
Mitochondrial aconitase reaction with nitric oxide, S-nitrosoglutathione, and peroxynitrite: mechanisms and relative contributions to aconitase inactivation.
V. Tórtora (2007)
Gene expression profiles of metabolic enzyme transcripts in Alzheimer's disease
W. M. Brooks (2007)
Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells.
H. Raza (2008)
Proteomic and oxidative stress analysis in human brain samples of Huntington disease.
M. A. Sorolla (2008)
Oxidative stress and neurotoxicity.
L. Sayre (2008)
Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment
F. Mangialasche (2009)
Redox proteomics identification of 4‐hydroxynonenal‐modified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesis
M. Perluigi (2009)
Oxidative Inactivation of Mitochondrial Aconitase Results in Iron and H2O2-Mediated Neurotoxicity in Rat Primary Mesencephalic Cultures
David Cantu (2009)
High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.
F. Mangialasche (2010)
Mitochondrial protein quality control systems in aging and disease.
Karin Luce (2010)
Mitochondrial protein quality control during biogenesis and aging.
B. M. Baker (2011)
Increased protein and lipid oxidative damage in mitochondria isolated from lymphocytes from patients with Alzheimer's disease: insights into the role of oxidative stress in Alzheimer's disease and initial investigations into a potential biomarker for this dementing disorder.
R. Sultana (2011)
Changes in mitochondrial glutathione levels and protein thiol oxidation in ∆yfh1 yeast cells and the lymphoblasts of patients with Friedreich's ataxia.
A. Bulteau (2012)
Tocopherols and tocotrienols plasma levels are associated with cognitive impairment
F. Mangialasche (2012)
Mitochondrial oxidative stress index, activity of redox-sensitive aconitase and effects of endogenous anti- and pro-oxidants on its activity in control, Alzheimer's disease and Swedish Familial Alzheimer's disease brain
M. Raukas (2012)
Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease.
R. Sultana (2013)
Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults
F. Mangialasche (2013)

This paper is referenced by
The Influence of Serum Uric Acid Level on Alzheimer's Disease: A Narrative Review
Mengyuan Qiao (2021)
Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses
Inseo Choi (2021)
Mitochondriopathies as a Clue to Systemic Disorders—Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine
A. Líšková (2021)
Shared perturbations in the metallome and metabolome of Alzheimer’s, Parkinson’s, Huntington’s, and dementia with Lewy bodies: A systematic review
Melissa Scholefield (2020)
Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease
D. Butterfield (2020)
Dauricine Attenuates Spatial Memory Impairment and Alzheimer-Like Pathologies by Enhancing Mitochondrial Function in a Mouse Model of Alzheimer's Disease
Chongyang Chen (2021)
Mitochondria and cellular redox state on the route from ageing to Alzheimer’s disease
G. Abate (2020)
GSK3‐ARC/Arg3.1 and GSK3‐Wnt signaling axes trigger amyloid‐β accumulation and neuroinflammation in middle‐aged Shugoshin 1 mice
C. Rao (2020)
Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease
Richard J. Johnson (2020)
Metabolic determinants of leukocyte pathogenicity in neurological diseases
Marah C Runtsch (2020)
Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update
G. Cenini (2019)
Zinc cooperates with p53 to inhibit the activity of mitochondrial aconitase through reactive oxygen species accumulation
Ya-Nan Xue (2019)
Iron-regulatory genes are associated with Neuroimaging measures in HIV infection
C. Fennema-Notestine (2020)
A meta-analysis of peripheral tocopherol levels in age-related cognitive decline and Alzheimer’s disease
S. Ashley (2019)
A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway
T. Berry (2019)
Redox Status, Procoagulant Activity, and Metabolome of Fresh Frozen Plasma in Glucose 6-Phosphate Dehydrogenase Deficiency
Vassilis L. Tzounakas (2018)
A Long Journey into Aging, Brain Aging, and Alzheimer’s Disease Following the Oxidative Stress Tracks1
P. Mecocci (2018)
Do low‐serum vitamin E levels increase the risk of Alzheimer disease in older people? Evidence from a meta‐analysis of case‐control studies
Y. Dong (2018)
Plasma Antioxidant Status in Patients with Alzheimer's Disease and Cognitively Intact Elderly: A Meta-Analysis of Case-Control Studies.
K. Mullan (2018)
Oxidant/Antioxidant Imbalance in Alzheimer's Disease: Therapeutic and Diagnostic Prospects
J. Wojsiat (2018)
Mitochondrial genes are altered in blood early in Alzheimer's disease
K. Lunnon (2017)
Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.
J. Savas (2017)
Molecular events linking cholesterol to Alzheimer's disease and inclusion body myositis in a rabbit model.
Q. Liu (2016)
Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls
S. Ayyadevara (2016)
Vitamin E family: Role in the pathogenesis and treatment of Alzheimer's disease
V. Boccardi (2016)
Review Article Vitamin E family: Role in the pathogenesis and treatment of Alzheimer's disease
V. Boccardi (2016)
Oxidative Stress and Aberrant Cell Cycle in Alzheimer's Disease Lymphocytes: Diagnostic Prospects.
Joanna Wojsiat (2015)
A novel gene selection method using GA/SVM and fisher criteria in Alzheimer's disease
Seyede Zahra Paylakhi (2015)
Semantic Scholar Logo Some data provided by SemanticScholar