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The Inside-Out Amyloid Hypothesis and Synapse Pathology in Alzheimer's Disease.

Gouras, Gunnar LU ; Willén, Katarina LU and Faideau, Mathilde LU (2014) In Neurodegenerative Diseases 13(2-3). p.142-146
Abstract
Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD) transgenic mouse models, as well as in human postmortem AD brains, highlights that age-related increases in β-amyloid peptide (Aβ), particularly in endosomes near synapses, are involved in early synapse dysfunction. Our immunoelectron microscopy and high-resolution immunofluorescence microscopy studies show that this early subcellular Aβ accumulation leads to progressive Aβ aggregation and pathology, particularly within dystrophic neurites and synapses. These studies confirm that neuritic/synaptic Aβ accumulation is the nidus of plaque formation. Aβ-dependent synapse pathology in AD models is modulated by synaptic activity and is plaque independent. The amyloid... (More)
Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD) transgenic mouse models, as well as in human postmortem AD brains, highlights that age-related increases in β-amyloid peptide (Aβ), particularly in endosomes near synapses, are involved in early synapse dysfunction. Our immunoelectron microscopy and high-resolution immunofluorescence microscopy studies show that this early subcellular Aβ accumulation leads to progressive Aβ aggregation and pathology, particularly within dystrophic neurites and synapses. These studies confirm that neuritic/synaptic Aβ accumulation is the nidus of plaque formation. Aβ-dependent synapse pathology in AD models is modulated by synaptic activity and is plaque independent. The amyloid precursor protein (APP) is normally transported down neurites and appears to be preferentially processed to Aβ at synapses. Synapses are sites of early Aβ accumulation and aberrant tau phosphorylation in AD, which alter the synaptic composition at early stages of the disease. Elucidating the normal role of APP, and potentially of Aβ, at synapses should provide important insights into the mechanism(s) of Aβ-induced synapse dysfunction in AD and how to therapeutically mitigate these dysfunctions. © 2013 S. Karger AG, Basel. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurodegenerative Diseases
volume
13
issue
2-3
pages
142 - 146
publisher
Karger
external identifiers
  • pmid:24080821
  • wos:000330752200023
  • scopus:84896847488
ISSN
1660-2862
DOI
10.1159/000354776
language
English
LU publication?
yes
id
347f0915-0478-446e-a51b-1d515c20bbbe (old id 4143809)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24080821?dopt=Abstract
date added to LUP
2013-11-02 19:59:50
date last changed
2017-01-22 03:06:13
@article{347f0915-0478-446e-a51b-1d515c20bbbe,
  abstract     = {Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD) transgenic mouse models, as well as in human postmortem AD brains, highlights that age-related increases in β-amyloid peptide (Aβ), particularly in endosomes near synapses, are involved in early synapse dysfunction. Our immunoelectron microscopy and high-resolution immunofluorescence microscopy studies show that this early subcellular Aβ accumulation leads to progressive Aβ aggregation and pathology, particularly within dystrophic neurites and synapses. These studies confirm that neuritic/synaptic Aβ accumulation is the nidus of plaque formation. Aβ-dependent synapse pathology in AD models is modulated by synaptic activity and is plaque independent. The amyloid precursor protein (APP) is normally transported down neurites and appears to be preferentially processed to Aβ at synapses. Synapses are sites of early Aβ accumulation and aberrant tau phosphorylation in AD, which alter the synaptic composition at early stages of the disease. Elucidating the normal role of APP, and potentially of Aβ, at synapses should provide important insights into the mechanism(s) of Aβ-induced synapse dysfunction in AD and how to therapeutically mitigate these dysfunctions. © 2013 S. Karger AG, Basel.},
  author       = {Gouras, Gunnar and Willén, Katarina and Faideau, Mathilde},
  issn         = {1660-2862},
  language     = {eng},
  number       = {2-3},
  pages        = {142--146},
  publisher    = {Karger},
  series       = {Neurodegenerative Diseases},
  title        = {The Inside-Out Amyloid Hypothesis and Synapse Pathology in Alzheimer's Disease.},
  url          = {http://dx.doi.org/10.1159/000354776},
  volume       = {13},
  year         = {2014},
}