Journal of Neural Transmission

, Volume 111, Issue 3, pp 295–310

(r)-, but not (s)-alpha lipoic acid stimulates deficient brain pyruvate dehydrogenase complex in vascular dementia, but not in Alzheimer dementia

  • L. Frölich
  • M. E. Götz
  • M. Weinmüller
  • M. B. H. Youdim
  • N. Barth
  • A. Dirr
  • W. Gsell
  • K. Jellinger
  • H. Beckmann
  • P. Riederer
Article

DOI: 10.1007/s00702-003-0043-5

Cite this article as:
Frölich, L., Götz, M., Weinmüller, M. et al. J Neural Transm (2004) 111: 295. doi:10.1007/s00702-003-0043-5

Summary.

In dementia of Alzheimer type (DAT), cerebral glucose metabolism is reduced in vivo, and enzymes involved in glucose breakdown are impaired in post-mortem brain tissue. Pyruvate dehydrogenase complex activity (PDHc) is one of the enzymes known to be reduced, while succinate dehydrogenase activity (SDH), another enzyme of oxidative glucose metabolism is unchanged. In dementia of vascular type (DVT), variable changes in glucose metabolism have been demonstrated in vivo, while changes of enzyme activities in post-mortem brain tissue are unknown. Here, PDHc and SDH activity were stimulated with each of the two stereoisomers of alpha lipoic acid in post-mortem parietal brain cortex of patients with DAT, DVT, and one case of Pick’s disease and compared to stimulation effects in a control group, matched for age, sex, post-mortem delay, and storage time of brain tissue. PDHc in DAT and DVT, but not in Pick’s disease was reduced. PDHc activity could be slightly stimulated by 10 µM of the physiological stereoisomer (r)-alpha-lipoic acid, in controls and DVT (possibly also in Pick’s disease), but not in DAT. In all groups investigated SDH was activated by 100 µM and 1 mM of both isomers of alpha-lipoic acid, whereas 10 mM of both stereoisomers of alpha-lipoic acid caused an inhibition of both, PDHc and SDH activity. The loss of basal and of (r)-alpha-lipoic acid stimulated PDHc activity indicate that a functional or structural impairment of PDHc may exist in DAT and DVT which is not merely attributable to loss of mitochondria since basal and stimulated SDH activities are similar in controls, DVT and DAT, thus indicating selective vulnerability of PDHc.

Keywords: Dementia of Alzheimer type, dementia of vascular type, pyruvate dehydrogenase complex, succinate dehydrogenase, alpha-lipoic acid, post-mortem human brain. 

Copyright information

© Springer-Verlag/Wien 2003

Authors and Affiliations

  • L. Frölich
    • 1
  • M. E. Götz
    • 2
    • 5
  • M. Weinmüller
    • 4
  • M. B. H. Youdim
    • 4
  • N. Barth
    • 2
  • A. Dirr
    • 2
  • W. Gsell
    • 2
  • K. Jellinger
    • 4
  • H. Beckmann
    • 2
  • P. Riederer
    • 2
  1. 1.Division of Geriatric PsychiatryCentral Institute of Mental Health Mannheim, University of HeidelbergGermany
  2. 2.Department of PsychiatryUniversity of WürzburgGermany
  3. 3.Pharmacology DepartmentTechnion InstituteIsrael
  4. 4.Ludwig Boltzmann Institute of Clinical NeurobiologyViennaAustria
  5. 5.Department of Pharmacology and ToxicologyUniversity of WürzburgGermany

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