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Related Experiment Videos

beta-Amyloid, protein processing and Alzheimer's disease

C Haas1, A Y Hung, M Citron

  • 1Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Arzneimittel-Forschung
|March 1, 1995
PubMed
Summary

Alzheimer's disease involves amyloid beta-peptide (A beta) buildup. This study reveals a novel pathway for A beta generation through endosomal/lysosomal processing of the beta-amyloid precursor protein (beta APP).

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Alzheimer's disease (AD) is characterized by amyloid beta-peptide (A beta) deposition.
  • A beta originates from the proteolytic processing of the beta-amyloid precursor protein (beta APP).
  • Conventional secretory processing of beta APP normally prevents A beta formation.

Purpose of the Study:

  • To describe an alternative processing pathway for beta APP.
  • To investigate the cellular mechanisms of A beta generation.
  • To provide a cellular model for studying familial AD mutations.

Main Methods:

  • Analysis of beta APP processing within isolated lysosomes.
  • Detection of secreted A beta in cultured cells.
  • Cell culture experiments with transfected mutant beta APP cDNA.

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Main Results:

  • Amyloidogenic fragments were identified within isolated lysosomes, suggesting precursors for A beta production.
  • Secreted A beta was detected in cell culture media.
  • A beta is secreted in vivo and detectable in human plasma and CSF.

Conclusions:

  • An alternative endosomal/lysosomal pathway for beta APP processing contributes to A beta generation.
  • This cellular system allows for the study of A beta molecular mechanisms and regulation.
  • The model facilitates analysis of familial AD-associated beta APP mutations.