Advertisement

Changes of intracellular calcium regulation in Alzheimer’s disease and vascular dementia

  • A. Eckert
  • H. Förstl
  • R. Zerfass
  • M. Oster
  • M. Hennerici
  • W. E. Müller
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 54)

Summary

Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer’s disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients. However, the findings are still controversial. Using blood lymphocytes and neutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD patients and non-demented controls. We found no major difference in Ca2+ homeostasis, since neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation indicating an impaired function of Ca2+ influx-controlling mechanisms. Furthermore, we studied whether differences exist in Ca2+ regulation between lymphocytes from patients with vascular dementia and AD patients, to define AD-specific alterations and to distinguish between the two dementia groups and non-demented control subjects respectively. First evidences indicate that Ca2+ mobilization in lymphocytes is specifically impaired in lymphocytes from patients with vascular dementia.

Keywords

Vascular Dementia Clinical Dementia Rating Free Intracellular Calcium Neurobiol Aging Intracellular Calcium Regulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adunsky A, Baram D, Hershkowitz M, Mekori YA (1991) Increased cytosolic calcium in lymphocytes of Alzheimer patients. J Neuroimmunol 33: 167–172PubMedCrossRefGoogle Scholar
  2. Araga S, Kagimoto H, Funamoto K, Takahashi K (1990) Lymphocyte proliferation and subpopulations in dementia of the Alzheimer’s type. Jpn J Med 29: 572–575PubMedCrossRefGoogle Scholar
  3. Bondy B, Klages U, Müller-Spahn F, Hock C (1994) Cytosolic free [Ca2+]i in mononuclear blood cells from demented patients and healthy controls. Eur Arch Psychiatry Clin Neurosci 243: 224–228PubMedCrossRefGoogle Scholar
  4. Bondy B, Hofmann M, Müller-Spahn F, Witzko M, Hock CH (1996) The PHA-induced calcium signal in lymphocytes is altered after blockade of K+ channels in Alzheimer’s disease. J Psychiat Res 30: 217–227PubMedCrossRefGoogle Scholar
  5. Borden LA, Maxfield FR, Goldman JE, Shelanski ML (1991) Resting [Ca2+]i and [Ca2+]i transients are similar in fibroblasts from normal and Alzheimer’s donors. Neurobiol Aging 13: 33–38CrossRefGoogle Scholar
  6. Collins JM, Scott RB, McClish DK, Taylor JR, Grogan WM (1991) Altered membrane anisotropy gradients of plasma membranes of living peripheral blood leukocytes in aging and Alzheimer’s disease. Mech Ageing Dev 59: 153–162PubMedCrossRefGoogle Scholar
  7. deLustig ES, Kohan S, Famulari AL, Dominguez RO, Serra JA (1994) Peripheral markers and diagnostic criteria in Alzheimer’s disease: critical evaluations. Rev Neurosci 5: 213–225PubMedGoogle Scholar
  8. Dysken MW, Minichielleo MD, Hill JL, Skare S, Little JT, Molchan SE, Sunderland T (1992) Distribution of peripheral lymphocytes in Alzheimer patients and controls. J Psychiat Res 26: 213–218PubMedCrossRefGoogle Scholar
  9. Eckert A, Hartmann H, Müller WE (1993a) β-Amyloid protein enhances the mitogen-induced calcium response in circulating human lymphocytes. FEBS Lett 330: 49–52PubMedCrossRefGoogle Scholar
  10. Eckert A, Försti H, Hartmann H, Müller WE (1993b) Decreased β-amyloid sensitivity in Alzheimer’s disease. Lancet 342: 805–806PubMedCrossRefGoogle Scholar
  11. Eckert A, Hartmann H, Försti H, Müller WE (1994) Alterations of intracellular calcium regulation during aging and Alzheimer’s disease in nonneuronal cells. Life Sci 55: 2019–2029PubMedCrossRefGoogle Scholar
  12. Eckert A, Försti H, Zerfass R, Hartmann H, Müller WE (1996) Lymphocytes and neutrophils as peripheral models to study the effect of β-amyloid on cellular calcium signalling in Alzheimer’s disease. Life Sci 59: 499’510PubMedCrossRefGoogle Scholar
  13. Eckert A, Föprsti H, Zerfass R, Hennerici M, Müller WE (1997a) Free intracellular calcium in peripheral cells in Alzheimer’s disease. Neurobiol Aging 18: 281–284PubMedCrossRefGoogle Scholar
  14. Eckert A, Oster M, Försti H, Hennerici M, Müller WE (1997b) Impaired calcium regulation in subcortical vascular encephalopathy. Stroke 28: 1351–1356PubMedCrossRefGoogle Scholar
  15. Gelfand EW, Cheung RK, Grinstein S (1984) Role of membrane potential in the regulation of lectin-induced calcium uptake. J Cell Physiol 121: 533–539PubMedCrossRefGoogle Scholar
  16. Gibson GE, Toral-Barza L (1992) Cytosolic free calcium in lymphoblasts from young, aged and Alzheimer’s subjects. Mech Ageing Dev 63: 1–9PubMedCrossRefGoogle Scholar
  17. Gottfries CG, Blennow K, Karlsson L, Wallin A (1994) The neurochemistry of vascular dementia. Dementia 5: 163–167PubMedGoogle Scholar
  18. Grossmann A, Kukull WA, Jinneman JC, Birds TD, Villacres EC, Larson EB, Rabinovitch PS (1993) Intracellular calcium response is reduced in CD44 lymphocytes in Alzheimer’s disease and in older persons with Down’s syndrome. Neurobiol Aging 14: 177–185PubMedCrossRefGoogle Scholar
  19. Hartmann H, Eckert A, Försti H, Müller WE (1994) Similar age-related changes of free intracellular calcium in lymphocytes and central neurons: effects of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 243: 218–223PubMedCrossRefGoogle Scholar
  20. Hartwig M (1995) Immune ageing and Alzheimer’s disease. NeuroReport 6: 1274–1276PubMedCrossRefGoogle Scholar
  21. O’Flaherty JT, Rossi AG, Jacobson DP, Redman JF (1991) Roles of Ca2+ in human neutrophils responses to receptor agonists. Biochem J 278: 705–711Google Scholar
  22. Peterson C, Ratan RR, Shelanski ML, Goldman JE (1986) Cytosolic free calcium and cell spreading decrease in fibroblasts from aged and Alzheimer donors. Proc Natl Acad Sci USA 83: 7999–8001PubMedCrossRefGoogle Scholar
  23. Tarkowski E, Naver H, Wallin BG, Blomstarnd C, Tarkowski A (1995) Lateralization of T-lymphocyte responses in patients with stroke. Stroke 26: 57–62PubMedCrossRefGoogle Scholar
  24. Weiss A, Littmann DR (1994) Signal transduction by lymphocyte antigen receptors. Cell 76: 263–274PubMedCrossRefGoogle Scholar
  25. Zweifach A, Lewis RS (1993) Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Natl Acad Sci USA 90: 6295–6299PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1998

Authors and Affiliations

  • A. Eckert
    • 1
    • 4
  • H. Förstl
    • 2
  • R. Zerfass
    • 2
  • M. Oster
    • 3
  • M. Hennerici
    • 3
  • W. E. Müller
    • 1
    • 4
    • 5
  1. 1.Departments of PsychopharmacologyCentral Institute of Mental HealthMannheimFederal Republic of Germany
  2. 2.Departments of PsychiatryCentral Institute of Mental HealthMannheimFederal Republic of Germany
  3. 3.Neurological ClinicKlinikum Mannheim of the University of HeidelbergMannheimFederal Republic of Germany
  4. 4.Department of Pharmacology, BiocenterUniversity of FrankfurtFrankfurtFederal Republic of Germany
  5. 5.Pharmakologisches Institut, BiozentrumUniversität FrankfurtFrankfurtFederal Republic of Germany

Personalised recommendations