Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide

Topic: Disease mechanisms in lab and animal studies

The accumulation in brain of senile plaques containing beta-amyloid protein (A beta) is a defining feature of Alzheimer's disease. The amyloid precursor protein (APP)4 from which A beta is derived is subject to several genetic mutations which segregate with rare familial forms of the disease, resulting in early onset of dementia and plaque formation, suggesting that APP metabolism plays a causal role in the disease. Various cell types have been shown to release a soluble form of A beta, thus allowing for the in vitro study of A beta generation. We report here evidence that a substantial portion of the APP secreted by human mixed brain cell cultures, as well as that present in cerebrospinal fluid, is of a novel form cleaved precisely at the amino terminus of A beta, suggesting that a secretory pathway is involved in A beta genesis.

Key findings

• The amyloid precursor protein (APP)4 from which A beta is derived is subject to several genetic mutations which segregate with rare familial forms of the disease, resulting in early onset of dementia and plaque formation, suggesting that APP metabolism plays a causal role in the disease.
• We report here evidence that a substantial portion of the APP secreted by human mixed brain cell cultures, as well as that present in cerebrospinal fluid, is of a novel form cleaved precisely at the amino terminus of A beta, suggesting that a secretory pathway is involved in A beta genesis.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1038/361260a0
• PubMed: 7678698
• Original source →

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@article{seubert1993-7678698,
  author  = {Seubert, P. and Oltersdorf, T. and Lee, M. G. and Barbour, R. and Blomquist, C. and Davis, D. L. and Bryant, K. and Fritz, L. C. and others},
  title   = {{Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide}},
  journal = {Nature},
  year    = {1993},
  doi     = {10.1038/361260a0},
  pmid    = {7678698},
  url     = {https://doi.org/10.1038/361260a0}
}

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