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The β-Amyloid Model of Alzheimer’s Disease

Conformation Change, Receptor Cross-Linking, and the Initiation of Apoptosis
  • Carl W. Cotman
  • David H. Cribbs
  • Aileen J. Anderson
Part of the Contemporary Neuroscience book series (CNEURO)

Abstract

In 1855, Virchow, looking for a link between plants and animals, discovered deposits of a substance in the brain that stained with iodine; he named this substance amyloid, after the Greek word for starch (1). The amyloid in these deposits was later identified as a peptide, and subsequently recognized as the major component of senile plaques in Alzheimer’s disease (AD). β-Amyloid (Aβ) has been used extensively to identify AD pathology. It was generally thought that Aβ itself was metabolically inert, lacking in biological activity, until recent studies with cultured neurons and other cells provided the first clear evidence that Aβ is an active peptide. Aβ has been shown to initiate neuronal degeneration and transiently enhance neuronal growth. These observations opened up the action of Aβ to extensive investigation and led to the key finding that the biological activity of Aβ is dependent on its transformation into a β-sheet conformation and related higher order molecular assemblies. This is of fundamental importance, because it suggests that the biological activity of Aβ is dependent on protein conformation and that the transition into this conformation generates a new biological activity. Indeed, the amount of Aβ that accumulates in the brain appears to correlate to the decline of brain function (2). The consequences of such a relationship between biological activity and protein conformation are critical to understanding the role of Aß and other β-pleated sheet protein assemblies, such as prion protein, in disease.

Keywords

Prion Protein Terminal Deoxynucleotidyl Transferase Postmortem Delay Initiate Cell Death Receptor Crosslinking 
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 1997

Authors and Affiliations

  • Carl W. Cotman
  • David H. Cribbs
  • Aileen J. Anderson

There are no affiliations available

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