Journal of Neurology

, Volume 240, Issue 6, pp 377–380 | Cite as

Analyses of energy metabolism and mitochondrial genome in post-mortem brain from patients with Alzheimer's disease

  • Heinz Reichmann
  • Stephanie Fhirke
  • Gert Hebenstreit
  • Hans Schrubar
  • Peter Riederer
Original Communications


Biochemical and mitochondrial DNA analyses were performed in post-mortem brain tissue from seven patients with dementia of Alzheimer's type and age- and sex-matched controls. We analysed all complexes of the respiratory chain in four regions, i.e. temporal, parietal, entorhinal cortex and hippocampus. Although enzymes representing complex II, III and IV were reduced in activity, succinate cytochrome c reductase was significantly reduced only in the parietal and temporal cortex. However, Southern blot analyses with two restriction enzymes excluded any deletions larger than 500 by in parietal and entorhinal cortex. It is concluded that there seems to be no specific respiratory chain defect in Alzheimer's disease.

Key words

Neurodegenerative diseases Alzheimer's disease Respiratory chain Mitochondrial genome Oxidative metabolism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anderson S, Banker AT, Barrell BG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465Google Scholar
  2. 2.
    Bindoff LA, Birch Machin M, Cartlidge NEF, Parker WDJ, Turnbull DM (1989) Mitochondrial function in Parkinson's disease. Lancet II:49Google Scholar
  3. 3.
    Brown GC, Levine SR, Gorell JM (1989) In vivo 32P NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia. Neurology 39:1423–1427Google Scholar
  4. 4.
    Foster NL, Chase TN, Mansi L (1984) Cortical abnormalities in Alzheimer's disease. Ann Neurol 16:649–654Google Scholar
  5. 5.
    Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminium and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol 31:286–292Google Scholar
  6. 6.
    Goto YJ, Nonaka J, Horai S (1990) A mutation in the tRNAleu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653Google Scholar
  7. 7.
    Götz ME, Freyberger A, Hauer E, Burger R, Sofic E, Gsell W, Heckers S, Jellinger K, Hebenstreit G, Frölich L, Beckmann H, Riederer P (1992) Susceptibility to oxygen-stimulated lipid peroxidation and differential scanning calorimetry of brains from patients with Alzheimer's disease. Dementia 3:213–222Google Scholar
  8. 8.
    Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717–719Google Scholar
  9. 9.
    Ikebe S, Tanaka M, Ohno K, Sato W, Hanori K, Kundo T, Mizuno Y, Ozawa T (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. Biochem Biophys Res Commun 170:1044–1048Google Scholar
  10. 10.
    Kemper T (1984) Neuroanatomical and neuropathological changes in normal aging and in dementia. In: Albert ML (ed) Clinical neurology of aging. Oxford University Press, New York, pp 9–52Google Scholar
  11. 11.
    King TE, Howard RL (1967) Preparation and properties of soluble NADH dehydrogenase from cardiac muscle. Methods Enzymol 10:275–294Google Scholar
  12. 12.
    Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet I:885Google Scholar
  13. 13.
    Lestienne P, Nelson I, Riederer P, Jellinger K, Reichmann H (1990) Normal mitochondrial genome in brain from patients with Parkinson's disease and complex I defect. J Neurochem 55:1810–1812Google Scholar
  14. 14.
    Lestienne P, Nelson I, Riederer P, Reichmann H, Jellinger K (1991) Mitochondrial DNA in postmortem brain from patients with Parkinson's disease. J Neurochem 56:1819Google Scholar
  15. 15.
    Lowry OH, Rosenbrough NJ, Farr AL (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  16. 16.
    Mizuno Y, Ohta S, Tanaka M, et al (1989) Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem Biophys Res Commun 163:1450–1455Google Scholar
  17. 17.
    Moreas CT, DiMauro S, Zeviani M, et al (1989) Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320:1293–1299Google Scholar
  18. 18.
    Parker WDJ, Filley CM, Parks JK (1990) Cytochrome oxidase deficiency in Alzheimer's disease. Neurology 40:1302–1303Google Scholar
  19. 19.
    Perry EK, Perry RH, Tomlinson BE, et al (1980) Coenzyme A-acetylating enzyme in Alzheimer's disease: possible cholinergic “compartment” of pyruvate dehydrogenase. Neurosci Lett 18:105–110Google Scholar
  20. 20.
    Pette D, Reichmann H (1982) A method for quantitative extraction of enzymes and metabolites from tissue samples in the milligram range. J Histochem Cytochem 30:401–402Google Scholar
  21. 21.
    Reichmann H (1988) Enzyme activity measured in single muscle fibers in partial cytochrome c oxidase deficiency. Neurology 38:244–249Google Scholar
  22. 22.
    Reichmann H, Hoppeler H, Matthieu-Costello O, et al (1985) Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflügers Arch 404:1–9Google Scholar
  23. 23.
    Reichmann H, Riederer P, Seufert S (1990) Disturbances of the respiratory chain in brain from patients with Parkinson's disease. Mov Disord 5:28Google Scholar
  24. 24.
    Reichmann H, Degoul F, Gold R, et al (1991) Histological, enzymatic, and mitochondrial DNA studies in patients with Kearns-Sayre syndrome and chronic progressive ophthalmoplegia. Eur Neurol 31:108–113Google Scholar
  25. 25.
    Schapira AHV, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 54:823–827Google Scholar
  26. 26.
    Shoffner JM, Lott MT, Lezza AMS, et al (1900) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNAlys mutation. Cell 61:931–937Google Scholar
  27. 27.
    Shoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC (1991) Mitochondrial oxidative phosphorylation defects in Parkinson's disease. Ann Neurol 30:332–339Google Scholar
  28. 28.
    Sims NR, Blass JP, Murphy C, Bowen DM, Neary D (1987) Phosphofructokinase activity in the brain in Alzheimer's disease. Ann Neurol 21:509–510Google Scholar
  29. 29.
    Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78Google Scholar
  30. 30.
    Sottocasa GL, Kuylenstierna B, Ernster L (1967) An electron transport system associated with the outer membrane of the mitochondria. J Cell Biol 32:415–438Google Scholar
  31. 31.
    Vanella A, Villa RF, Gorini A, Campisi A, Giuffrida-Stella AM (1989) Superoxide dismutase and cytochrome oxidase activities in light and heavy synaptic mitochondria from rat cerebral cortex during aging. J Neurosci Res 22:351–355Google Scholar
  32. 32.
    Wallace DC, Zheng Y, Lott MT, et al (1988) Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55:601–610Google Scholar
  33. 33.
    Wharton DC, Tzagoloff A (1967) Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10:245–250Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Heinz Reichmann
    • 1
  • Stephanie Fhirke
    • 1
  • Gert Hebenstreit
    • 3
  • Hans Schrubar
    • 1
  • Peter Riederer
    • 2
  1. 1.Department of NeurologyUniversity of WürzburgWürzburgGermany
  2. 2.Department of Psychiatry, Division of NeurochemistryUniversity of WürzburgWürzburgGermany
  3. 3.Department of Psychiatry, LKHAmstetten/MauerAustria

Personalised recommendations