nach oben

Erschienen in:

01.09.2011 | Original Paper

Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease

verfasst von: Pollyana Feldhaus, Daiane B. Fraga, Fernando V. Ghedim, Renata D. De Luca, Thiago D. Bruna, Matheus Heluany, Maria Paula Matos, Gabriela K. Ferreira, Isabela C. Jeremias, Claudia Heluany, Emilio L. Streck, Alexandra I. Zugno

Erschienen in: Metabolic Brain Disease | Ausgabe 3/2011

Einloggen, um Zugang zu erhalten

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disease associated with cognitive impairment in multiple domains, such as memory and executive functions. Studies reveal damage in the electron transport chain of patients with AD, suggesting that this mitochondrial dysfunction plays an important role in the pathophysiology of the disease. Blood samples were taken from patients with AD (n = 20) and older subjects without dementia (n = 40) to evaluate the activity of complexes I, II, II–III, and IV of the mitochondrial respiratory chain in isolated lymphocytes. Results from the patient and control groups were compared. The activity of complexes II and IV was increased among patients compared to the control group. No significant difference was observed between controls who were not using psychotropic medication and patients. Our findings point out a mechanism of cellular compensation in which the mitochondrial respiratory chain requires an increase in electron transport to supply the energy needed for cellular functioning. Additional studies are needed to better clarify the mechanisms involved in the mitochondrial dynamics of AD.

Aleardi AM, Benard G, Augereau O, Malgat M, Talbot JC, Mazat JP, Letellier T, Dachary-Prigent J, Solaini GC, Rossignol R (2005) Gradual alteration of mitochondrial structure and function by beta-amyloids: importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release. J Bioenerg Biomembr 37:207–225PubMedCrossRef

Aliev G, Smith MA, de la Torre JC, Perry G (2004) Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer’s disease. Mitochondrion 4:649–663PubMedCrossRef

Almeida OP (1998) Mini exame do estado mental e o diagnóstico de demência no Brasil. Arq Neuro Psiquiatr 56:605–612CrossRef

Atamina H, Frey WH (2007) Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease. Mitochondria 7:297–310CrossRef

Baloyannis SJ, Costa V, Michmizos D (2004) Mitochondrial alterations in Alzheimer’s disease. Am J Alzheimers Dis Other Demen 19:89–93PubMedCrossRef

Bonilla E, Tanji K, Hirano M, Vu TH, Dimauro S, Schon EA (1999) Mitochondrial involvement in Alzheimer’s disease. Biochim Biophys Acta 1410:171–182PubMedCrossRef

Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Murri L, Rapoport SI, Solaini G (2002) Cytochrome c oxidase and mitochondrial F₁F₀-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease. Neurobiol Aging 23:371–376PubMedCrossRef

Brucki SMD, Malheiros SMF, Okamoto IH, Bertolucci PHF (1997) Dados normativos para o teste de fluência verbal categoria animais em nosso meio. Arq Neuro Psiquiatr 55:56–61CrossRef

Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH (2003) Sugestões para o uso do mini-exame do estado mental no Brasil. Arq Neuro Psiquiatr 61:777–781CrossRef

Brunnstrom HR, Englund EM (2009) Cause of death in patients with dementia disorders. Eur J Neurol 16:488–492PubMedCrossRef

Brzyska M, Elbaum D (2003) Dysregulation of calcium in Alzheimer’s disease. Acta Neurobiol Exp 63:171–183

Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer’s brain: mechanistic implications. Ann Neurol 57:695–703PubMedCrossRef

Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stem D, McKhann G, Yan SD (2005) Mitochondrial abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. J Fed Am Soc Exp Biol 19:2040–2041

Cassin A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316CrossRef

Chen X, Yan SD (2006) Mitochondrial Aβ: a potential cause of metabolic dysfunction in Alzheimer’s disease. IUBMB Life 58:686–694PubMedCrossRef

Coskun PE, Beal MF, Wallace DC (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Natl Acad Sci USA 101:10726–10731CrossRef

Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005) Cooper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-β₁₋₄₂. J Neurosci 25:672–679PubMedCrossRef

Cummings JL, Schneider L, Tariot PN, Kershaw PR, Yuan W (2004) Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease. Am J Psychiatr 161:532–538PubMedCrossRef

Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R (1997) Effects of age, sex and ethnicity on the association between apolipoprotein E genotype and Alzheimer’s disease. A meta-analysis. APOE and Alzheimer’s disease meta analysis consortium. J Am Med Assoc 278:1349–1356CrossRef

Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Jansen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–26PubMedCrossRef

Fukui H, Moraes CT (2008) The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 31:251–256PubMedCrossRef

Galimberti D, Scarpini E (2010) Treatment of Alzheimer’s disease: symptomatic and disease-modifying approaches. Curr Aging Sci 3:46–56PubMedCrossRef

Gibson GE, Sheu KFR, Blass JP (1998) Abnormalities of mitochondrial enzymes in Alzheimer’s disease. J Neural Transm 105:855–870PubMedCrossRef

Keil U, Hauptmann S, Bonert A, Scherping I, Eckert A, Müller WE (2006) Mitochondrial dysfunction induced by disease relevant AβPP and tau protein mutations. J Alzheim Dis 9:139–146

Kristofiková Z, Bocková M, Hegnerová K, Bartos A, Klaschka J, Rícný J, Rípová D, Homola J (2009) Enhanced levels of mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis. Mol Biosyst 5:1174–1179PubMedCrossRef

Laar VSV, Berman SB (2009) Mitochondrial dynamics in Parkinson’s disease. Exp Neurol 218:247–256PubMedCrossRef

Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedCrossRef

Mandavilli BS, Santos JH, Houten BV (2002) Mitochondrial DNA repair and aging. Mutat Res 509:127–151PubMed

Markesbery WR, Kryscio RJ, Lovell MA, Morrow JD (2005) Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann Neurol 58:730–735PubMedCrossRef

Maruszak A, Zekanowki C (2011) Mitochondrial dysfunction and Alzheimer’s disease. Progr Neuro Psychopharmacol Biol Psychiatr 35:320–330CrossRef

Maurer I, Zierz S, Möller HJ (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer’s disease patients. Neurobiol Aging 21:455–462PubMedCrossRef

Moreira PI, Santos MS, Oliveira CR (2007) Alzheimer’s disease: a lesson from mitochondrial dysfunction. Antiox Red Sign 9:1621–1630CrossRef

Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol 292:670–686CrossRef

Nitrini R (1999) Epidemiologia da doença de Alzheimer no Brasil. Ver de Psiqu Clín 26

Nitrini R, Caramelli P, Bottino CMC, Damasceno BP, Brucki SMD, Anghinah R (2005) Diagnóstico de doença de Alzheimer no Brasil: avaliação cognitiva e funcional. Arq Neuro Psiquiatr 63:720–727CrossRef

Onyango IG, Khan SM (2006) Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer’s disease. Curr Alzheimer Res 3:339–349PubMedCrossRef

Ozawa T (1998) Mitochondrial DNA mutations and age. Ann N Y Acad Sci 854:128–154PubMedCrossRef

Parihar MS, Hemmani T (2004) Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci 11:456–467PubMedCrossRef

Parker WD Jr, Parks J, Filley CM, Kleinscmidt-DeMasters BK (1994) Electron transport chain defects in Alzheimer’s disease brain. Neurology 44:1090–1096PubMed

Pérez-Gracia E, Torrejón-Escribano B, Ferrer I (2008) Dystrophic neurites of senile plaques in Alzheimer’s disease are deficient in cytochrome c oxidase. Acta Neuropathol 116:261–268PubMedCrossRef

Reddy PH (2007) Mitochondrial dysfunction in aging and Alzheimer’s disease: strategies to protect neurons. Antiox Red Sign 9:1647–1658CrossRef

Reddy PH (2008) Mitochondrial medicine for aging and neurodegenerative diseases. Neuromol Med 10:291–315CrossRef

Reddy PH (2009) Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer’s disease. Exp Neurol 218:286–292PubMedCrossRef

Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 14:45–53PubMedCrossRef

Rogaeva E (2002) The solved and unsolved mysteries of the genetics of early-onset Alzheimer’s disease. Neuromol Med 2:1–10CrossRef

Rustin P, Chretien D, Bourgeron T, Gérard B, Rötig A, Saudubray JM, Munnich A (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228:35–51PubMedCrossRef

Santos RX, Correia SC, Wang X, Perry G, Smith MA, Moreira PI, Zhu X (2010) A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease. J Alzheim Dis 20:401–412

Sereniki A, Vital MABF (2008) A doença de Alzheimer: aspectos fisiopatológicos e farmacológicos. Rev de Psiq do Rio Grande do Sul 30

Shulman KI, Shedletsky R, Silver IL (1986) The challenge of time: clock-drawing and cognitive function in elderly. Int J Ger Psych 1:135–140CrossRef

Silva KCA, Lourenço RA (2008) Tradução, adaptação e validação de construto do Teste do Relógio aplicado entre idosos no Brasil. Rev Saúde Púb 42:930–937CrossRef

Spreen O, Strauss E (1998) A compendium of neuropsychological tests: administration, norms, and commentary. Oxford University Press, New York

Strazielle C, Jazi R, Verdier Y, Qian S, Lalonde R (2009) Regional brain metabolism with cytochrome c oxidase histochemistry in a PS1/A246E mouse model of autosomal dominant Alzheimer’s disease: Correlations with behavior and oxidative stress. Neurochem Int 55:806–814PubMedCrossRef

Strazielle C, Sturchler-Pierrat C, Staufenbiel M, Lalonde R (2003) Regional brain cytochrome oxidase activity in β-Amyloid precursor protein transgenic mice with the Swedish mutation. Neuroscience 118:1151–1163PubMedCrossRef

Sunderland T, Hill JL, Mellow AM, Lawlor BA, Gundersheimer J, Newhouse PA, Grafman JH (1989) Clock drawing in Alzheimer disease: a novel measure of dementia severity. J Am Geriat Soc 37:725–729PubMed

Swerdlow RH (2002) Mitochondrial DNA-related mitochondrial dysfunction in neurodegenerative diseases. Arch Pathol Lab Med 126:271–280PubMed

Swerdlow RH (2007) Pathogenesis of Alzheimer’s disease. Clin Interv Aging 2:347–359PubMed

Swedlow RH, Burns JM, Khan SM (2010) The Alzheimer’s disease mitochondrial cascade hypothesis. J Alzheim Dis 20:265–279

Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypothesis 63:8–20CrossRef

Swerdlow RH, Kish SJ (2002) Mitochondria in Alzheimer’s disease. Int Rev Neurobiol 53:341–385PubMedCrossRef

Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer’s patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21:4923–4930PubMed

Valla J, Schneider L, Niedzielko T (2006) Impaired platelet mitochondrial activity in Alzheimer’s disease and mild cognitive impairment. Mitochondria 6:323–330CrossRef

Vargas T, Ugalde C, Spuch C, Antequera D, Morán MJ, Martín MA, Ferrer I, Bermejo-Pareja F, Carro E (2010) Aβ accumulation in choroid plexus is associated with mitochondrial-induced apoptosis. Neurobiol Aging 31:1569–1581PubMedCrossRef

Wang X, Su B, Lee H, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondria fission and fusion in Alzheimer’s disease. J Neurosci 29:9090–9103PubMedCrossRef

Young KJ, Bennett JP (2010) The mitochondrial secret(ase) of Alzheimer’s disease. J Alzheim Dis 20:381–400

Titel: Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease
verfasst von: Pollyana Feldhaus
Daiane B. Fraga
Fernando V. Ghedim
Renata D. De Luca
Thiago D. Bruna
Matheus Heluany
Maria Paula Matos
Gabriela K. Ferreira
Isabela C. Jeremias
Claudia Heluany
Emilio L. Streck
Alexandra I. Zugno
Publikationsdatum: 01.09.2011
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 3/2011
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-011-9253-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2011

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India

Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats

Effects of oxcarbazepine on monoamines content in hippocampus and head and body shakes and sleep patterns in kainic acid-treated rats

Behavioral and neurochemical effects of proline

David W. McCandless (1941–2011): A personal tribute