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

Gouras, Gunnar LU ; Willén, Katarina LU and Tampellini, Davide LU (2012) In Life Sciences 91(23-24). p.1153-1158
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, Alzheimer's disease, Intraneuronal, Prion, Detergent
in
Life Sciences
volume
91
issue
23-24
pages
1153 - 1158
publisher
Elsevier
external identifiers
  • wos:000312170900005
  • scopus:84869506753
ISSN
1879-0631
DOI
10.1016/j.lfs.2012.06.004
language
English
LU publication?
yes
id
891f532b-2183-4164-9f75-26450722a92b (old id 3367030)
date added to LUP
2013-02-01 06:58:08
date last changed
2017-01-22 03:16:54
@article{891f532b-2183-4164-9f75-26450722a92b,
  abstract     = {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.},
  author       = {Gouras, Gunnar and Willén, Katarina and Tampellini, Davide},
  issn         = {1879-0631},
  keyword      = {Amyloid,Alzheimer's disease,Intraneuronal,Prion,Detergent},
  language     = {eng},
  number       = {23-24},
  pages        = {1153--1158},
  publisher    = {Elsevier},
  series       = {Life Sciences},
  title        = {Critical role of intraneuronal A beta in Alzheimer's disease: Technical challenges in studying intracellular A beta},
  url          = {http://dx.doi.org/10.1016/j.lfs.2012.06.004},
  volume       = {91},
  year         = {2012},
}