The β‐Amyloid Precursor Protein (APP) and Alzheimer's Disease: Does the Tail Wag the Dog?

  title={The $\beta$‐Amyloid Precursor Protein (APP) and Alzheimer's Disease: Does the Tail Wag the Dog?},
  author={Edward H. Koo},
  • E. Koo
  • Published 1 September 2002
  • Biology, Chemistry
  • Traffic
The β‐amyloid precursor protein has been the focus of much attention from the Alzheimer's disease community for the past decade and a half. The β‐amyloid precursor protein holds a pivotal position in Alzheimer's disease research because it is the precursor to the amyloid β‐protein which many believe plays a central role in Alzheimer's disease pathogenesis. It was also the first gene in which mutations associated with inherited Alzheimer's disease were found. Although the molecular details of… 

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Calnuc binds to Alzheimer’s β‐amyloid precursor protein and affects its biogenesis

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The amyloid precursor protein (APP)‐cytoplasmic fragment generated by γ‐secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture

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Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.

  • E. KooS. Sisodia D. Price
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
It is suggested that APP is synthesized in neurons and delivered to dystrophic nerve endings, where subsequent alterations of local processing of APP result in deposits of brain amyloid.

Alzheimer's disease: genes, proteins, and therapy.

Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.

A second cytotoxic proteolytic peptide derived from amyloid β-protein precursor

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β-Secretase Processing in the Trans-Golgi Network Preferentially Generates Truncated Amyloid Species That Accumulate in Alzheimer's Disease Brain*

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Intracellular routing of human amyloid protein precursor: Axonal delivery followed by transport to the dendrites

Results suggest that the newly synthesized APP, after initial axonal delivery, may be transported to the dendrites by a transcytotic mechanism, arguing for neuronal specific sorting and processing mechanisms.