Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.

Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study...

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Autores principales:	Willem de Haan, Katherine Mott, Elisabeth C W van Straaten, Philip Scheltens, Cornelis J Stam
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5e6033ca571a4359abd2e59099bb3e0b
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spelling	oai:doaj.org-article:5e6033ca571a4359abd2e59099bb3e0b2021-11-18T05:51:06ZActivity dependent degeneration explains hub vulnerability in Alzheimer's disease.1553-734X1553-735810.1371/journal.pcbi.1002582https://doaj.org/article/5e6033ca571a4359abd2e59099bb3e0b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22915996/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. 'Activity dependent degeneration' (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration. Resulting structural and functional network changes were assessed with graph theoretical analysis. Effects of ADD included oscillatory slowing, loss of spectral power and long-range synchronization, hub vulnerability, and disrupted functional network topology. Observed transient increases in spike density and functional connectivity match reports in Mild Cognitive Impairment (MCI) patients, and may not be compensatory but pathological. In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks. The insight that neuronal activity might play a causal role in Alzheimer's disease can have implications for early detection and interventional strategies.Willem de HaanKatherine MottElisabeth C W van StraatenPhilip ScheltensCornelis J StamPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 8, p e1002582 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Willem de Haan Katherine Mott Elisabeth C W van Straaten Philip Scheltens Cornelis J Stam Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
description	Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. 'Activity dependent degeneration' (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration. Resulting structural and functional network changes were assessed with graph theoretical analysis. Effects of ADD included oscillatory slowing, loss of spectral power and long-range synchronization, hub vulnerability, and disrupted functional network topology. Observed transient increases in spike density and functional connectivity match reports in Mild Cognitive Impairment (MCI) patients, and may not be compensatory but pathological. In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks. The insight that neuronal activity might play a causal role in Alzheimer's disease can have implications for early detection and interventional strategies.
format	article
author	Willem de Haan Katherine Mott Elisabeth C W van Straaten Philip Scheltens Cornelis J Stam
author_facet	Willem de Haan Katherine Mott Elisabeth C W van Straaten Philip Scheltens Cornelis J Stam
author_sort	Willem de Haan
title	Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
title_short	Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
title_full	Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
title_fullStr	Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
title_full_unstemmed	Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.
title_sort	activity dependent degeneration explains hub vulnerability in alzheimer's disease.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5e6033ca571a4359abd2e59099bb3e0b
work_keys_str_mv	AT willemdehaan activitydependentdegenerationexplainshubvulnerabilityinalzheimersdisease AT katherinemott activitydependentdegenerationexplainshubvulnerabilityinalzheimersdisease AT elisabethcwvanstraaten activitydependentdegenerationexplainshubvulnerabilityinalzheimersdisease AT philipscheltens activitydependentdegenerationexplainshubvulnerabilityinalzheimersdisease AT cornelisjstam activitydependentdegenerationexplainshubvulnerabilityinalzheimersdisease
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Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.

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