{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzp4be\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzp4be\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/15\\\/13\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/15\\\/13\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/15\\\/13\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/15\\\/13\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EEven though they have distinct clinical, pathologic, and biochemical features, Parkinson\u0027s disease (PD), Alzheimer\u0027s disease (AD), Huntington\u0027s disease, and less commonly prion disease are all characterized by misfolded protein aggregation in the brain and fatal neuronal loss. The unfolded protein response (UPR) is emerging as a common player in all neurodegenerative diseases. This article discusses a study that is investigating changes in the UPR pathway in deceased subjects with PD with dementia (PDD) and dementia with Lewy bodies in comparison with patients with AD and control subjects.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDementias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExtrapyramidal \u0026amp; Movement Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDementias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExtrapyramidal \u0026amp; Movement Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EEven though they have distinct clinical, pathologic, and biochemical features, Parkinson\u0027s disease (PD), Alzheimer\u0027s disease (AD), Huntington\u0027s disease, and less commonly prion disease are all characterized by misfolded protein aggregation in the brain and fatal neuronal loss. The unfolded protein response (UPR) is emerging as a common player in all neurodegenerative diseases. Misfolded proteins in the endoplasmic reticulum (ER) trigger the dissociation of the ER chaperone GRP78\/BiP from protein kinase ribonucleic acid\u2013 like ER kinase and other proteins, activating the UPR stress response. Initially the UPR is neuroprotective, but prolonged activation and failure to restore protein homeostasis can lead to neurodegeneration.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EEvidence of UPR activation in both AD and PD suggests that the neurons are subjected to ER stress, but no studies have investigated the UPR in patients who have dementia with PD and AD pathology. The aim of this study, presented by Jean-Ha Baek, PhD, Karolinska Institute, Huddinge, Sweden, was to investigate changes in the UPR pathway in deceased subjects with PD with dementia (PDD) and dementia with Lewy bodies (DLB) in comparison with patients with AD and control subjects.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPostmortem brain tissue from 4 brain regions was provided by Brains for Dementia Research, United Kingdom, for evaluation (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14550\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14550\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14550\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003ENumber and Type of Brain Tissue Samples\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EGRP78\/BiP protein levels were quantified with western blot to measure the degree of UPR activation. Binding immunoglobulin protein (GRP78\/BiP) expression patterns were assessed with immunohistochemistry.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EBrain tissue from the cingulate gyrus of patients with PDD and those with DLB had a significant increase in the level of GRP78\/BiP protein compared with tissue from patients with AD and control subjects (p=0.000 for all comparisons). GRP78\/BiP protein expression in the parietal cortex was significantly decreased in brain tissue from patients with AD compared with control subjects (p=0.000) and significantly increased in tissue from patients with PDD compared with patients with AD (p=0.002) and in patients with DLB compared with those with AD (p=0.001). No significant differences were observed in GRP78\/BiP levels in the prefrontal cortex and temporal cortex between any of the brain tissue sample groups.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EImmunohistochemical studies detected GRP78\/BiP protein in the cytoplasm of prefrontal cortex neurons in brain tissue from patients with AD, PDD, and DLB and controls. Although the labeling intensity was slightly increased in AD, PDD, and DLB patient samples compared with controls, the intensity was similar across the different disease groups.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThis was the first study to investigate changes in the UPR pathway in deceased subjects with PDD and DLB in comparison with patients with AD and control subjects. Pearson correlation analysis found no association between changes in the GRP78\/BiP protein level and Mini-Mental State Examination scores before death, rate of decline in Mini-Mental State Examination score, or global and regional pathologic scores for \u03b1-synuclein, plaques, and tangles. There was no correlation of Hoehn and Yahr scores with GRP78\/BiP levels in a subset of subjects with PDD.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/15\/13.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp4be\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzp4be\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}