NPTX2 and cognitive dysfunction in Alzheimer’s Disease
dc.contributor.author | Xiao, M | |
dc.contributor.author | Xu, D | |
dc.contributor.author | Craig, MT | |
dc.contributor.author | Pelkey, KA | |
dc.contributor.author | Chien, C | |
dc.contributor.author | Shi, Y | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Resnick, S | |
dc.contributor.author | Pletnikova, O | |
dc.contributor.author | Salmon, D | |
dc.contributor.author | Brewer, J | |
dc.contributor.author | Edland, S | |
dc.contributor.author | Wegiel, J | |
dc.contributor.author | Tycko, B | |
dc.contributor.author | Savonenko, A | |
dc.contributor.author | Reeves, RH | |
dc.contributor.author | Troncoso, JC | |
dc.contributor.author | McBain, CJ | |
dc.contributor.author | Galasko, D | |
dc.contributor.author | Worley, PF | |
dc.date.accessioned | 2017-05-24T15:25:46Z | |
dc.date.issued | 2017-03-23 | |
dc.description.abstract | Memory loss in Alzheimer’s disease (AD) is attributed to pervasive weakening and loss of synapses. Here, we present findings supporting a special role for excitatory synapses connecting pyramidal neurons of the hippocampus and cortex with fast-spiking parvalbumin (PV) interneurons that control network excitability and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA receptor subunit GluA4, which is regulated by presynaptic expression of the synaptogenic immediate early gene NPTX2 by pyramidal neurons. In a mouse model of AD amyloidosis, Nptx2-/- results in reduced GluA4 expression, disrupted rhythmicity, and increased pyramidal neuron excitability. Postmortem human AD cortex shows profound reductions of NPTX2 and coordinate reductions of GluA4. NPTX2 in human CSF is reduced in subjects with AD and shows robust correlations with cognitive performance and hippocampal volume. These findings implicate failure of adaptive control of pyramidal neuron-PV circuits as a pathophysiological mechanism contributing to cognitive failure in AD. | en_GB |
dc.description.sponsorship | DNA.This study was supported by NIMH MH100024 (PFW), (R35 NS-097966) (PFW), P50 AG005146-27 (PFW, JCT), Down Syndrome Research and Treatment Foundation and Research Down Syndrome (MX and RR), NIA AG05131 (DS, SE, DG), Alzheimer’s Disease Drug Discovery Foundation (DX, DG) and in part by the Intramural Research Program, National Institute on Aging, and National Institutes on Child Health and Development, NIH. | en_GB |
dc.identifier.citation | Vol. 6, article e23798 | en_GB |
dc.identifier.doi | 10.7554/eLife.23798 | |
dc.identifier.uri | http://hdl.handle.net/10871/27683 | |
dc.language.iso | en | en_GB |
dc.publisher | eLife Sciences Publications | en_GB |
dc.rights | Copyright Xiao et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited: https://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.subject | immediate early gene | en_GB |
dc.subject | inhibitory neuron | en_GB |
dc.subject | dementia | en_GB |
dc.subject | Alzheimer's disease | en_GB |
dc.title | NPTX2 and cognitive dysfunction in Alzheimer’s Disease | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-05-24T15:25:46Z | |
dc.contributor.editor | Chao, MV | en_GB |
dc.identifier.issn | 2050-084X | |
dc.description | This is the final version of the article. Available from eLife Sciences Publications via the DOI in this record. | en_GB |
dc.identifier.journal | eLife | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ |
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Except where otherwise noted, this item's licence is described as Copyright Xiao et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited: https://creativecommons.org/licenses/by/4.0/