Journal of Molecular Neuroscience

, Volume 20, Issue 2, pp 203–206 | Cite as

The relationship between amyloid and tau

Brief Communication

Abstract

Based on genetic findings, the relationship between the APP/Aβ and tau/tangle pathologies are discussed. It is argued that APP/Aβ is upstream of tau/tangle in the Alzheimer pathogenesis, and that the relationship between the pathologies are promiscuous in two ways: first, APP/Aβ can equally be seen to be upstream of synuclein/Lewy bodies in cell death pathways, and second, tau pathology can be initiated by genetic lesions in other pathways.

Index Entries

Amyloid plaques tangles tau, genetic Alzheimer’s disease Pick’s disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bales K. R., Verina T., Cummins D. J., et al. (1999) Apolipoprotein E is essential for amyloid deposition in the APP (V717F) transgenic mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 96, 15,233–15,238.CrossRefGoogle Scholar
  2. Brook J. D., McCurrach M. E., Harley, H. G., et al. (1992). Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3-prime end of a transcript encoding a protein kinase family member. Cell 68, 799–808.PubMedCrossRefGoogle Scholar
  3. Carstea E. D., Morris J. A., Coleman, K. G., et al. (1997) Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277, 228–231.PubMedCrossRefGoogle Scholar
  4. Games D., Adams D., Alessandrini R., et al. (1995). Alzheimer-type neuropathology in transgenic mice overexpressing V717F Beta-amyloid precursor protein. Nature 373, 523–527.PubMedCrossRefGoogle Scholar
  5. Goate A. M., Chartier-Harlin M. C., Mullan M. C., et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349, 704–706.PubMedCrossRefGoogle Scholar
  6. Goedert M., Jakes R., Spillantini M. G., Hasegawa M., Smith M. J., and Crowther R. A. (1996) Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 383, 550–553.PubMedCrossRefGoogle Scholar
  7. Hardy J. (1997) Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci. 20, 154–159.PubMedCrossRefGoogle Scholar
  8. Hardy, J. (1999) Pathways to primary neurodegenerative disease. Mayo Clinic Proc. 74, 835–837.Google Scholar
  9. Hsiao K., Dlouhy S. R., Farlow M. R., et al. (1992) Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with neurofibrillary tangles. Nat. Genet. 1, 68–71.PubMedCrossRefGoogle Scholar
  10. Lantos P. L., Ovenstone I. M., Johnson J., Clelland C. A., Roques P., and Rossor M. N. (1994) Lewy bodies in the brain of two members of a family with the 717 (Val to Ile) mutation of the amyloid precursor protein gene. Neurosci. Lett. 172, 77–79.PubMedCrossRefGoogle Scholar
  11. Leissring M. A., Akbari Y., Fanger, C. M., Cahalan M. D., Mattson M. P., and LaFerla F. M. (2000) Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knock in mice. J. Cell Biol. 149, 793–798.PubMedCrossRefGoogle Scholar
  12. Levy-Lahad E., Wasco W., Poorkaj P., et al. (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269, 973–977.PubMedCrossRefGoogle Scholar
  13. Lippa C. F., Fujiwara H., Mann D. M., et al. (1998) Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimer’s disease patients with mutations in presenilin and amyloid precursor protein genes. Am. J. Pathol. 153, 1365–1370.PubMedGoogle Scholar
  14. Mori H., Kondo T., Yokochi M., et al., (1998) Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology, 51, 890–892.PubMedGoogle Scholar
  15. Myers A., Holmans P., Marshall H., et al., (2000) Susceptibility locus for Alzheimer’s disease on chromosome 10. Science 290, 2304–2305.PubMedCrossRefGoogle Scholar
  16. Sherrington R., Rogaev E. I., Liang Y., et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375, 754–760.PubMedCrossRefGoogle Scholar
  17. Vidal R., Frangione B., Rostagno A., Mead S., Revesz T., Plant G., and Ghiso J. (1994) A stop-codon mutation in the BRI gene associated with familial British dementia. Nature 399, 776–781.Google Scholar
  18. Wavrant-De Vrieze F., Crook R., Holmans P., et al. (1999). Genetic variability at the amyloid-beta precursor protein locus may contribute to the risk of late-onset Alzheimer’s disease. Neurosci. Lett. 269, 67–70.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Laboratory of NeurogeneticsNIA/NIHBethesdaUSA

Personalised recommendations