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Research Article

Vol. 8 No. 1 (2004)

A Molecular Analysis Of Prion Protein Expression In Alzheimer's Disease

  • Alisdair McNeill
DOI
https://doi.org/10.26443/mjm.v8i1.519
Submitted
November 5, 2020
Published
2020-12-01

Abstract

In Prion Diseases, misfolding of neuronal prion protein (PrPC) to a pathogenic isomer (PrPSC) is associated with neuronal death. Previous pathological studies have demonstrated increased immunoreactivity of PrPC at Aβ plaques in Alzheimer's Disease, and it has been suggested that this either reflects a role for PrPC in the neuronal response to stress or is a feature of the neuropathogenesis of atypical subtypes of Alzheimer's disease. In this paper we utilised western blotting to examine the molecular characteristics of PrP in frozen Hippocampal tissue from 7 cases of Alzheimer's Disease in which prion protein expression was demonstrated by immunohistochemistry, before using Restriction Fragment Length Polymorphism (RFLP) methodology to define the genotype of the codon 129 polymorphism of PRNP in each case. We observed PrP accumulating as globular structures at A plaques, and within ependymal cells lining the lateral ventricle. Immunohistochemistry also showed that PrPC and Superoxide dismutase-1 where deposited in a similar pattern at Aβ plaques. Western blotting revealed that PrP in Alzheimer's disease is composed of the same 208-residue peptide expressed in non-diseased brain. Quantitative western blot analysis demonstrated increased levels of PrPC in a short duration case of Alzheimer's Disease, while, in the remaining cases, levels of PrPC decreased in parallel with increasing disease duration and decreasing brain mass. RFLP genotyping revealed that all codon 129 genotypes (M/M, M/V, V/V) were represented in our study cohort. Our data suggest that increased levels of PrPC may account for PrP immunoreactivity at plaques in Alzheimer's disease, and that PrP deposition is not restricted to certain atypical subtypes of Alzheimer's disease.

References

  1. Ironside JW. Prion Diseases In Man. Journal of Pathology 186(3):227-234; 1998.
  2. Collinge J, Whittington MA, Sidle KC, et al. Prion Protein Is Necessary For Normal Synaptic Function. Nature 370(6487):295-297; 1994.
  3. Herms J, Tings T, Gall S, et al. Evidence Of Presynaptic Location And Function Of The Prion Protein. Journal of Neuroscience 19(20): 8866-8875; 1999.
  4. Moore RC, Lee IY, Silverman GL, et al. Ataxia In Prion Protein Deficient Mice Is Associated With Upregulation Of The Novel PrP - Like Protein Doppel. Journal of Molecular Biology 292(4):797-817; 1999.
  5. Brown DR, Besinger A. Prion Protein And Superoxide Dismutase Activity. Biochemical Journal 334:423-429; 1998.
  6. Brown DR, Schulz - Schaeffer WJ, Schmidt B, Kretzschmar HA. Prion Protein Deficient Cells Show Altered Response To Oxidative Stress Due To Decreased SOD -1 Activity. Experimental Neurology 146(1):104-112; 1997.
  7. Voigtlander T, Kloppel S, Birner P, et al. Marked Increase Of Neuronal Prion Protein Immunoreactivity In Alzheimer's Disease And Human Prion Diseases. Acta Neuropathologica 101(5):417-423; 2001.
  8. Ferrer I, Blanco R, Carmona M, et al. Prion Protein Expression In Senile Plaques In Alzheimer's Disease. Acta Neuropathologica 101(1):49-56; 2001.
  9. Perry RT, Go RCP, Harrell LE, et al. SSCP Analysis And Sequencing Of The Prion Protein Gene Detects Two 24 bp Deletions In An Atypical Alzheimer's Disease Family. American Journal of Medical Genetics 60(1):12-18; 1995.
  10. Casadei VM, Ferri C, Calabrese E, et al. Prion Protein Gene Polymorphism And Alzheimer's Disease: One Modulatory Trait of Cognitive Decline? Journal of Neurology, Neurosurgery and Psychiatry 71(2):279-280; 2001
  11. Leuba G, Saini K, Savioz A, Charnay Y. Early Onset Familial Alzheimer Disease With Co-existing -Amyloid And Prion Pathology. Journal of the American Medical Association 283(13):756; 2000.
  12. Graham DI, Lantos PL. Ageing And Dementia. In: Graham DI, Lantos PL, eds. Greenfield's Neuropathology. London: Arnold, 1997.
  13. Lyras L, Cairns NJ, Jenner A, Jenner P, Halliwell B. An Assessment Of Oxidative Damage To Proteins, Lipids, And DNA In Brain From Patients With Alzheimer's Disease. Journal of Neurochemistry 68(5):2061-2069; 1997.
  14. Yatin SM, Aksenova M, Aksenov M, et al. Temporal relations among amyloid beta-peptide-induced free-radical oxidative stress, neuronal toxicity, and neuronal defensive responses. Journal of Molecular Neuroscience 11(3):183-97; 1998.
  15. Celsi F, Ferri A, Casciati A, et al. Overexpression of SOD-1 Protects Against -Amyloid Peptide Toxicity: Effect of Oestrogen and Copper Chelators. Neurochemistry International 44(1):25-33; 2004.
  16. McLennan NF, Rennison KA, Bell JE, Ironside JW. In Situ Hybridisation Analysis Of PrP mRNA In Human CNS Tissue. Neuropath. Applied Neurobiology 27(5):373-383; 2001.
  17. DeArmond SJ. Alzheimer's Disease and Creutzfeldt-Jakob Disease: Overlap Of Pathogenic Mechanisms. Currents Opinions in Neurology 6(6):872-881; 1993.
  18. Hainfellner JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H. Coexistance Of Alzheimer-Type Neuropathology In Creutzfeldt Jakob Disease. Acta Neuropathologica 96(2):116-122; 1998.
  19. Forloni G, Tagliavini F, Bugiani O, Salmona M. Amyloid in Alzheimer's Disease And Prion Related Encephalopathies: Studies With Synthetic Peptides. Progress in Neurobiology 49(4):287-315; 1996.
  20. Dickson DW. The Pathogenesis of Senile Plaques. Journal of Neuropathology and Experimental Neurology 56(4):321-339; 1997.
  21. Kovacs GG, Zerbi P, Voigtlander T, et al. The Prion Protein In Human Neurodegenerative Disorders. Neuroscience Letters 329(3):269-272; 2002.

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