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Critical role of intraneuronal A beta in Alzheimer's disease: Technical challenges in studying intracellular A beta

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Author

Summary, in English

Aims: Multiple lines of evidence have implicated beta-amyloid (A beta) in the pathogenesis of Alzheimer's disease (AD). However, the mechanism(s) whereby A beta is involved in the disease process remains unclear. The dominant hypothesis in AD has been that A beta initiates the disease via toxicity from secreted, extracellular A beta aggregates. More recently, an alternative hypothesis has emerged focusing on a pool of A beta that accumulates early on within AD vulnerable neurons of the brain. Although the topic of intraneuronal A beta has been of major interest in the field, technical difficulties in detecting intraneuronal A beta have also made this topic remarkably controversial. Here we review evidence pointing to the critical role of intraneuronal A beta in AD and provide insights both into challenges faced in detecting intracellular A beta and the prion-like properties of A beta. Main methods: Immunoprecipitation and Western blot are used for A beta detection. Key findings: We highlight that a standard biochemical method can underestimate intraneuronal A beta and that extracellular A beta can up-regulate intracellular A beta. We also show that detergent can remove intraneuronal A beta. Significance: There is a growing awareness that intraneuronal A beta is a key pathogenic pool of A beta involved in causing synapse dysfunction. Difficulties in detecting intraneuronal A beta are an insufficient reason for ignoring this critical pool of A beta. (C) 2012 Elsevier Inc. All rights reserved.

Publishing year

2012

Language

English

Pages

1153-1158

Publication/Series

Life Sciences

Volume

91

Issue

23-24

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Keywords

  • Amyloid
  • Alzheimer's disease
  • Intraneuronal
  • Prion
  • Detergent

Status

Published

Research group

  • Experimental Dementia Research

ISBN/ISSN/Other

  • ISSN: 1879-0631