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:
https://lup.lub.lu.se/record/4143809
- author
- Gouras, Gunnar
LU
; Willén, Katarina
LU
and Faideau, Mathilde
LU
- organization
- publishing date
- 2014
- 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
- pmid:24080821
- 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
- 2016-04-01 10:12:31
- date last changed
- 2022-05-05 19:42:32
@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}},
doi = {{10.1159/000354776}},
volume = {{13}},
year = {{2014}},
}