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Normal Production of the Amyloid β-Protein and the Pathogenesis of Alzheimer’s Disease

  • Dennis J. Selkoe
  • Christian Haass
  • Michael Schlossmacher
  • Albert Hung
  • Martin Citron
  • David Teplow
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)

Abstract

Progressive cerebral dysfunction in Alzheimer’s disease and Down’s syndrome is accompanied by the formation of innumerable extracellular amyloid deposits in the form of senile plaques and microvascular amyloid. The amyloid fibrils are composed of the 39–43 residue amyloid (ß-protein (Aß), a fragment of the integral membrane polypeptide, ß-amyloid precursor protein (ßAPP). Evidence from several laboratories has shown that amorphous, largely nonfilamentous deposits of Aß (“diffuse or ”preamyloid“ plaques) precede the development of fibrillary amyloid, dystrophic neuntes, neurofibrillary tangles, and other cytopathological changes in Down’s syndrome and, by inference, in Alzheimer’s disease. This finding suggests that ß-amyloidosis, like certain other amyloidoses, does not occur secondary to local cellular pathology (e.g., dystrophic neurites) but rather precedes it. The clearest evidence that the processing of ßAPP into Aß can actually cause Alzheimer’s disease has come from the identification by several laboratories of missense mutations in the ßAPP gene within and flanking the Aß region in affected members of certain families having Alzheimer’s disease or hereditary cerebral hemorrhage with amyloidosis of the Dutch type.

Keywords

Amyloid Fibril pAPP Processing Dystrophic Neurites Hereditary Cerebral Hemorrhage Dutch Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Dennis J. Selkoe
    • 1
  • Christian Haass
    • 1
  • Michael Schlossmacher
    • 1
  • Albert Hung
    • 1
  • Martin Citron
    • 1
  • David Teplow
    • 1
  1. 1.Center for Neurologic DiseasesHarvard Medical School Brigham and Women’s HospitalBostonUSA

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