Abstract
THE accumulation in brain of senile plaques containing β-amyloid protein (Aβ) is a defining feature of Alzheimer's disease1–3. The amyloid precursor protein (APP)4 from which Aβ 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 formation5–9, suggesting that APP metabolism plays a causal role in the disease. Various cell types have been shown to release a soluble form of Aβ, thus allowing for the in vitro study of Aβ generation10–12. 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 Aβ, suggesting that a secretory pathway is involved in Aβ genesis.
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Seubert, P., Oltersdorf, T., Lee, M. et al. Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide. Nature 361, 260–263 (1993). https://doi.org/10.1038/361260a0
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DOI: https://doi.org/10.1038/361260a0
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