Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis

Neuronal activity has a strong causal role in the production and release of the neurotoxic β-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβ into amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elev...

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Main Authors: Annabella Pignataro, Silvia Middei
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2017/5281829
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author Annabella Pignataro
Silvia Middei
author_facet Annabella Pignataro
Silvia Middei
author_sort Annabella Pignataro
collection DOAJ
description Neuronal activity has a strong causal role in the production and release of the neurotoxic β-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβ into amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between Aβ and activity is not always linear and recent studies report exceptions to the view of “more activity, more plaques.” Here, we review the literature about the activity-dependent production of Aβ in both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to Aβ accumulation. Next, we will examine data supporting the hypothesis that, since Aβ is released from synaptic terminals, β-amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to Aβ accumulation. Finally, we consider possible mechanisms that account for β-amyloidosis progression through synaptically linked regions.
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spelling doaj-art-e3499bbb943740e896ec67e54743e2102025-08-20T02:21:24ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/52818295281829Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-AmyloidosisAnnabella Pignataro0Silvia Middei1Department of Experimental Neurology, Laboratory of Psychobiology, Santa Lucia Foundation, Via del Fosso di Fiorano, 00143 Rome, ItalyDepartment of Experimental Neurology, Laboratory of Psychobiology, Santa Lucia Foundation, Via del Fosso di Fiorano, 00143 Rome, ItalyNeuronal activity has a strong causal role in the production and release of the neurotoxic β-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβ into amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between Aβ and activity is not always linear and recent studies report exceptions to the view of “more activity, more plaques.” Here, we review the literature about the activity-dependent production of Aβ in both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to Aβ accumulation. Next, we will examine data supporting the hypothesis that, since Aβ is released from synaptic terminals, β-amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to Aβ accumulation. Finally, we consider possible mechanisms that account for β-amyloidosis progression through synaptically linked regions.http://dx.doi.org/10.1155/2017/5281829
spellingShingle Annabella Pignataro
Silvia Middei
Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
Neural Plasticity
title Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
title_full Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
title_fullStr Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
title_full_unstemmed Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
title_short Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis
title_sort trans synaptic spread of amyloid β in alzheimer s disease paths to β amyloidosis
url http://dx.doi.org/10.1155/2017/5281829
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