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:
https://lup.lub.lu.se/record/3367030
- author
- Gouras, Gunnar
LU
; Willén, Katarina
LU
and Tampellini, Davide
LU
- organization
- publishing date
- 2012
- 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
- pmid:22727791
- 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
- 2016-04-01 10:57:14
- date last changed
- 2022-05-13 21:40:04
@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}},
keywords = {{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}},
doi = {{10.1016/j.lfs.2012.06.004}},
volume = {{91}},
year = {{2012}},
}