Medical Hypotheses
Volume 57, Issue 2 , Pages 156-160 , August 2001

Alzheimer’s disease: roles for mitochondrial damage, the hydroxyl radical, and cerebrospinal fluid deficiency of melatonin

Received 30 October 2000 ,Accepted 9 January 2001.

References 

    REFERENCES
  1. Maurizi CP. Loss of intraventricular fluid melatonin can explain the neuropathology of Alzheimer’s disease. Med Hypotheses. 1997;49:153–158
  2. Markesbery W. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med. 1997;23:134–147
  3. Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr. 2000;71(suppl):621S–629S
  4. Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta. 2000;1502:139–144
  5. Albers DS, Beal MF. Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. J Neurol Transm. 2000;59:133–154
  6. Takeda A, Smith MA, Avila J. In Alzheimer’s disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification. J Neurochem. 2000;75:1234–1241
  7. Blass JP, Baker AC, Ko L, Black RS. Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation. Arch Neurol. 1990;47:864–869
  8. Tan D-X, Manchester LC, Reiter RJ, Qi W-B, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: Reactions and products. Biol Signal Recept. 2000;9:137–159
  9. Skinner DC, Malpaux B. High melatonin concentrations in the third ventricular cerebrospinal fluid are not due to Galen vein blood recirculating through the choroid plexus. Endocrinology. 1999;140:4399–4405
  10. Maurizi CP. A cycle of cerebrospinal fluid: supporting evidence and theoretical considerations. Med Hypotheses. 2000;54:417–422
  11. Van Hoesen GW. Ventromedial temporal lobe anatomy with comments on Alzheimer’s disease and temporal injury. J Neuropsychiatry Clin Neuroci. 1997;9:331–341
  12. Lui R, Zhou J, van Heerikhuize J, Hofman MA, Swaab DF. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease and apolipoprotein E- e 4/4. J Clin Endocrinol Metab. 1999;84:323–327
  13. Ehhalt DH. Radical ideas. Science. 1998;279:1002–1003
  14. Fischer T, Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin. Influence of the application time point. Biol Signals Recept. 1999;8:31–35
  15. Karbownik M, Reiter R. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med. 2000;225:9–22
  16. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJA. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem. 1990;263:16330–16336
  17. Maurer I, Zierz S, Moller HJ. A selective defect of cytochrome c oxidase is present in brain of Alzheimer’ disease patients. Neurobiol Aging. 2000;21:455–462
  18. Verwer RW, Jansen KA, Sluiter AA, Pool CW, Kamphorst W, Swaab DF. Decreased hippocampal metabolic activity in Alzheimer patients is not reflected in the immunoreactivity of cytochrome oxidase subunits. Exp Neurol. 2000;163:440–451
  19. Redjems-Bennani N, Jeandel C, Lefebvre E, Blain H, Vidailhet M. Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients. Gerontology. 1998;44:300–304
  20. Curti D, Rognoni F, Gasparini L. Oxidative metabolism in cultured fibroblasts derived for sporadic Alzheimer’s disease (AD) patients. Neurosci Lett. 1997;236:13–16
  21. Halliwell B. Oxidants and the central nervous system: some fundamental questions. Acta Neurol Scand. 1989;126:23–33
  22. Smith MA, Harris PLR, Sayre LM, Perry G. Iron accumulation in Alzheimer’s disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA. 1997;94:9866–9868
  23. Martin M, Macias M, Escames G, Leon J, Acuna-Castroviejo D. Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl hydroperoxide induced mitochondrial oxidative stress. FASEB J. 2000;14:1677–1679
  24. Martin M, Macias M, Escames G. Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res. 2000;28:242–248
  25. Jean-Louis G, von Gizychi H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res. 1998;25:177–183
  26. Brusco LI, Marques M, Cardinali DP. Monozygotic twins with Alzheimer’s disease treated with melatonin: Case report. J Pineal Res. 1998;25:260–263
  27. Cardinali, D. P. (personal communication).
  28. Brusco LI, Marques M, Cardinali DP. Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer’s disease. Neuroendocrionology Lett. 1998;19:111–115
  29. Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly persons with dementia – a preliminary study. Arch Gerontol Gertiatr. 2000;31:65–76
  30. Maurizi CP. A preliminary understanding of mania: roles for melatonin, vasotocin and rapid-eye-movement sleep. Med Hypotheses. 2000;54:26–29

PII: S0306-9877(01)91324-6

doi: 10.1054/mehy.2001.1324

Medical Hypotheses
Volume 57, Issue 2 , Pages 156-160 , August 2001

Article Tools