6533b7d4fe1ef96bd1262aa0

RESEARCH PRODUCT

Lymphocytic Mitochondrial Aconitase Activity is Reduced in Alzheimer's Disease and Mild Cognitive Impairment

Mauro BaglioniRoberta CecchettiCarmelinda RuggieroMiia KivipeltoPatrizia MecocciDanilo PiobbicoRoberto MonasteroStefano BrancorsiniLothar KussmaulFrancesca Mangialasche

subject

MalePathologyantioxidantAntioxidantmedicine.medical_treatmentLymphocyteMitochondrionmedicine.disease_causePolymerase Chain ReactionPathogenesisVitamin Eoxidative stressLymphocytesaconitase (aconitate hydratase)Aconitate Hydratasereactive oxygen speciesGeneral NeuroscienceACO2General MedicineAlzheimer's diseasemitochondriaPsychiatry and Mental healthClinical Psychologyantioxidantsmedicine.anatomical_structureDisease ProgressionSettore MED/26 - NeurologiaFemaleAlzheimer diseaseAlzheimer's diseaseAzheimer diseasereactive nitrogen speciemedicine.medical_specialtyaconitase (aconitate hydratase); Alzheimer disease; antioxidants; free radicals; lymphocyte; mild cognitive impairment; mitochondria; oxidative stress; reactive nitrogen species; reactive oxygen speciesBlotting Westernfree radicalslymphocytemild cognitive impairmentInternal medicinemedicineHumansCognitive DysfunctionRNA MessengerAgedfree radicaloxidative strebusiness.industryVitamin EAconitasimedicine.diseasereactive nitrogen speciesEndocrinologyGeriatrics and GerontologyAlzheimer's disease; Aconitasi; oxidative stress; Aconitase (aconitate hydratase) Azheimer disease antioxidants free radicals lymphocyte mild cognitive impairment mitochondria oxidative stress reactive nitrogen species reactive oxygen speciesMental Status SchedulebusinessBiomarkersOxidative stress

description

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 radicalmediated 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.

yearjournalcountryeditionlanguage
2015-01-01Journal of Alzheimer's Disease
https://doi.org/10.3233/jad-142052