Amyloid Precursor Protein APP

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Amyloid Precursor Protein (APP)

• The effects of overproduction in Alzheimers and
  Downs Syndrome

Taylor Griffith, Rachel Christman, Shanley
Besett, Christa Franz
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Downs Syndrome

• trisomy 21
• poor neuron growth
• early neuron death
• an inability to produce new synapses (an
  important component of learning)

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APP Lecture Connection

• APP is an integral transmembrane protein coded
  for on chromosome 21
• Other genes code for proteases that normally
  cleave this protein into smaller peptides used
  for cell signaling
• cell movement in embryonic development, synapse
  formation neural plasticity
• normal apoptosis (programmed cell death)
• repair following neural injury
• However, elevated levels of APP (and therefore
  the products of cleavage) can lead to disease

p. 283
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Over Expression of APP

• With abnormal levels of APP, as seen in Downs
  Syndrome (trisomy 21) and Alzheimers, these
  cleaved peptides accumulate in the ECF and can
  impede normal neural growth, repair, cell
  signaling, and differentiation
• These deposits of peptides are called amyloid
  plaques (shown below)
• These plaques lead to the death of neurons
  especially in the hippocampus which is the major
  center for learning and memory

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Membrane Protein ? Plaque
Integral transmembrane protein
Proteases lyse APP into components that enter
either the ICF or ECF

Cut pieces of APP aggregate in ECF as amyloid
plaque and can signal cell death
Figures retrieved 4/16/08 http//www.rienstraclin
ic.com/newsletter/2006/2006Nov.html
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AnalogyThe Deadliest Catch

• APP are like boats in the ocean
• Some boats are good to control crab population
  but if there are too many, too many crabs die and
  pollution accumulates
• Pollutionplaques
• Crabs Neurons
• BoatsAPP

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References

• Isacson, O., Seo, H., Lin, L., Albeck D.,
  Granholm A. (2002). Alzheimers disease and
  Downs syndrome roles of APP, trophic factors
  and ACh. Trends in Neurosciences, 25, 79-82.
• Priller, C., Bauer T., Mitteregger G., Krebs, B.,
  Kretzschmar, H. A., Herms, J. (2006). Synapse
  formation and function is modulated by the
  amyloid precursor protein. Journal of
  Neuroscience, 26, 7212-7221.
• Salehi, A. (2006). Down Syndrome Cause of
  neuronal death in down syndrome, Alzheimers
  disease could be surprisingly simple. Biotech
  Week, p. 494.
• Turner, P.R., OConnor, K., Tate, W. P., Abraham,
  W.C. (2003) Roles of amyloid precursor protein
  and its fragments in regulation neural activity,
  plasticity, and memory. Programming Neurobiology,
  70, 1-32.
• Busciglio, J., Pelsman, A., Wong, C., Pigino, G.,
  Yuan, M., Mori, H . (2002). Altered metabolism
  of the amyloid ß precursor protein is associated
  with mitochondrial dysfunction in Downs
  syndrome. Neuron, 33, 677-688.
• Selkoe, D. J. (1998). The cell biology of
  ß-amyloid precursor protein and presenilin in
  Alzheimers disease. Cell Biology, 8, 447-453.
• Strooper, B. D. Annaert, W. (2000). Proteolytic
  processing and cell biological functions of the
  amyloid precursor protein. Journal of Cell
  Science, 113, 1857-1870.
• Ober, W. C., Garrison, C. W., Silverthorn A. C.,
  Johnson, B.R. (2007). Human Physiology An
  Integrated Approach, Fourth Edition. San
  Francisco Pearson.
• Lodish, H., Berk, A., Kaiser, C. A., Krieger, M.,
  Scott, M. P., Bretscher, A., et. al. (2008).
  Molecular Cell Biology Sixth Edition. New York
  W.H. Freeman and Company