The Non-Amyloid-β Component of Alzheimer’s Disease Plaque Amyloid: Comparative Analysis Suggests a Normal Function as a Synaptic Plasticizer

  • Julia M. George
  • David F. Clayton
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)


A second intrinsic peptide component of Alzheimer’s Disease amyloid has recently been identified and called the “Non-Amyloid-β Component” (NAC)1. The peptide’s precursor (NACP) is the homologue of a brain-specific presynaptic protein of unknown function, identified independently in at least four other laboratories. The first report of this protein was in 1988 by Maroteaux et al.2, who identified it as a component enriched in a biochemical preparation of synaptic vesicles from the electric organ of Torpedo. Later, they cloned related sequences from the rat, and showed them to be enriched in telencephalic regions of the rat brain3. They originally termed this protein “synuclein,” although early evidence for nuclear localization2 has yet to be corroborated. Nakajo and colleagues identified a closely-related protein, first in bovine brain4 and then from rats5. They showed this protein to be phosphorylated on serine residues, and have suggested it is also phosphorylated on tyrosine6; they named the protein Phosphoneuroprotein-14-kDa (PNP-14). More recently, Jakes et al.7, using an antibody originally raised against paired helical filaments, detected two forms of the same human protein, one more closely related to PNP-14 and the other more related to the original synuclein. Consistent among all these reports has been the observation that the protein(s) is especially abundant in the telencephalon (especially the hippocampus) where it is distinctly enriched in presynaptic elements2, 7–10.


Amyloid Fibril Zebra Finch Electric Organ Paired Helical Filament Song Learning 
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  1. 1.
    K. Ueda, et al., Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease, Proc. Natl. Acad. Sci. (USA) 90:11282 (1993).CrossRefGoogle Scholar
  2. 2.
    L. Maroteaux, J. Campanelli, and R. Scheller, Synuclein: a neuron-specific protein localized to the nucleus and presynaptic terminal, J. Neurosci. 8:2804 (1988).PubMedGoogle Scholar
  3. 3.
    L. Maroteaux, and R. Scheller, The rat brain synucleins; family of proteins transiently associated with neuronal membrane, Mol. Brain Res. 11:335 (1991).PubMedCrossRefGoogle Scholar
  4. 4.
    S. Nakajo, K. Omato, T. Aiuchi, T. Shibayama, I. Okahashi, H. Ochiai, Y. Nakai, K. Nakaya, and Y. Nakamura, Purification and characterization of a novel brain-specific 14-kDa protein, J. Neuropathol. 55:2031 (1990).Google Scholar
  5. 5.
    T. Tobe, S. Nakajo, A. Tanaka, A. Mitoya, K. Omata, K. Nakaya, M. Tomita, and Y. Nakamura, Cloning and characterization of the cDNA encoding a novel brain-specific 14-kDA protein, J. Neuropathol. 59:1624 (1992).Google Scholar
  6. 6.
    S. Nakajo, K. Tsukada, K. Omata, Y. Nakamura, and K. Nakaya, A new brain-specific 14-kDa protein is a phosphoprotein: its complete amino acid sequence and evidence for phosphorylation, Eur. J. Biochem. 217:1057 (1993).PubMedCrossRefGoogle Scholar
  7. 7.
    R. Jakes, M. Spillantini, and M. Goedert, Identification of two distinct synucleins from human brain, FEBS Let. 345:27 (1994).CrossRefGoogle Scholar
  8. 8.
    A. Iwai, E. Masliah, M. Yoshimoto, N. Ge, L. Flanagan, H. Rohan de Silva, A. Kittel, and T. Saitoh, The precursor protein of Non-Aβ Component of Alzheimer’s Disease Amyloid is a presynaptic protein of the central nervous system, Neuron 14:467 (1995).PubMedCrossRefGoogle Scholar
  9. 9.
    T. Shibayama-Imazu, I. Okahashi, K. Omata, S. Nakajo, H. Ochiai, Y. Nakai, T. Hama, Y. Nakamura, and K. Nakaya, Cell and tissue distribution and developmental change of neuron specific 14 kDa protein (phosphoneuroprotein 14), Brain Res. 622:17 (1993).PubMedCrossRefGoogle Scholar
  10. 10.
    S. Nakajo, S. Shioda, Y. Nakai, and K. Nakaya, Localization of phosphoneuroprotein 14 (PNP 14) and its mRNA expression in rat brain determined by immunocytochemistry and in situ hybridization, Mol. Brain Res. 27:81 (1994).PubMedCrossRefGoogle Scholar
  11. 11.
    J.M. George, H. Jin, W.S. Woods, and D.F. Clayton, Characterization of a novel protein regulated during the critical period for song learning in the zebra finch, (submitted).Google Scholar
  12. 12.
    J.M. George, H. Jin, W. Woods, and D.F. Clayton, A novel RNA is transiently induced in the song circuit of zebra finches during the critical period for song acquisition, Soc. Neurosci. Abstr. 19:807 (1993).Google Scholar
  13. 13.
    D.F. Clayton, M. Huecas, and K.L. Nastiuk, Analysis of preferential gene expression in the song control nucleus HVc of canaries, Soc. Neurosci. Abstr. 14:605 (1988).Google Scholar
  14. 14.
    D.F. Clayton, M.E. Huecas, E.Y. Sinclair-Thompson, K.L. Nastiuk, and F. Nottebohm, Probes for rare mRNAs reveal distributed cell subsets in canary brain, Neuron 1:249 (1988).PubMedCrossRefGoogle Scholar
  15. 15.
    S.-H. Han, C. Hulette, A.M. Saunders, G. Einstein, M. Pericak-Vance, W.J. Strittmatter, A.D. Roses, and D.E. Schmechel, Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer’s Disease and in age-matched controls, Exp. Neurol. 128:13 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    S.-H. Han, G. Einstein, K.H. Weisgraber, W.J. Strittmatter, A.M. Saunders, M. Pericak-Vance, A.D. Roses, and D.E. Schmechel, Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study, Journal of Neuropathol Exp Neurol 53:535 (1994).CrossRefGoogle Scholar
  17. 17.
    H.Y. Han, P.H. Weinreb, and P.T. Lansbury, The core Alzheimers peptide NAC forms amyloid fibrils which seed and are seeded by beta-amyloid — is NAC a common trigger or target in neurodegenerative disease, Chemistry & Biology 2:163 (1995).CrossRefGoogle Scholar
  18. 18.
    E. Corder, A. Saunders, W. Strittmatter, D. Schmechel, P. Gaskell, G. Small, A. Roses, J. Haines, and M. Pericak-Vance, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families, Science 261:921 (1993).PubMedCrossRefGoogle Scholar
  19. 19.
    D. Campion, et al., The NACP/Synuclein gene — chromosomal assignment and screening for alterations in Alzheimer disease, Genomics 26:254 (1995).PubMedCrossRefGoogle Scholar
  20. 20.
    X.H. Chen, et al., The Human NACP/Alpha-Synuclein gene — chromosome assignment to 4q21.3-Q22 and TaqI RFLP analysis, Genomics 26:425 (1995).PubMedCrossRefGoogle Scholar
  21. 21.
    M.C. Irizarry, T.W. Kim, R.E. Tanzi, D. Rosene, J.M. George, D.F. Clayton, and B.T. Hyman, Characterization of Synelfin/Synuclein/NACP in the central nervous system of Alzheimer’s Disease patients, (in prep.).Google Scholar
  22. 22.
    J.M. George, and D.F. Clayton, Differential regulation in the avian song control circuit of an mRNA predicting a highly conserved protein related to protein kinase C and the bcr oncogene, Mol. Brain Res. 12:323 (1992).PubMedCrossRefGoogle Scholar
  23. 23.
    G. Withers, J. George, G. Banker, and D.F. Clayton, Antibodies to HAT-3, a novel songbird protein, recognize synaptic elements in cultured rat hippocampal neurons., Soc. Neurosci. Abstr. 20:1437 (1994).Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Julia M. George
    • 1
  • David F. Clayton
    • 1
  1. 1.Department of Cell & Structural Biology and The Beckman InstituteUniversity of IllinoisUrbanaUSA

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