000154223 001__ 154223
000154223 005__ 20230915094029.0
000154223 0247_ $$2doi$$a10.1016/j.bbi.2020.05.070
000154223 0247_ $$2ISSN$$a0889-1591
000154223 0247_ $$2ISSN$$a1090-2139
000154223 0247_ $$2altmetric$$aaltmetric:83277713
000154223 0247_ $$2pmid$$apmid:32479993
000154223 037__ $$aDZNE-2021-00084
000154223 041__ $$aEnglish
000154223 082__ $$a150
000154223 1001_ $$aUnger, M. S.$$b0
000154223 245__ $$aCD8+ T-cells infiltrate Alzheimer’s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice
000154223 260__ $$aOrlando, Fla.$$bAcademic Press$$c2020
000154223 3367_ $$2DRIVER$$aarticle
000154223 3367_ $$2DataCite$$aOutput Types/Journal article
000154223 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1685016346_32152
000154223 3367_ $$2BibTeX$$aARTICLE
000154223 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000154223 3367_ $$00$$2EndNote$$aJournal Article
000154223 520__ $$aNeuroinflammation is a major contributor to disease progression in Alzheimer’s disease (AD) and is characterized by the activity of brain resident glial cells, in particular microglia cells. However, there is increasing evidence that peripheral immune cells infiltrate the brain at certain stages of AD progression and shape disease pathology. We recently identified CD8+ T-cells in the brain parenchyma of APP-PS1 transgenic mice being tightly associated with microglia as well as with neuronal structures. The functional role of CD8+ T-cells in the AD brain is however completely unexplored. Here, we demonstrate increased numbers of intra-parenchymal CD8+ T-cells in human AD post-mortem hippocampus, which was replicated in APP-PS1 mice. Also, aged WT mice show a remarkable infiltration of CD8+ T-cells, which was more pronounced and had an earlier onset in APP-PS1 mice. To address their functional relevance in AD, we successfully ablated the pool of CD8+ T-cells in the blood, spleen and brain from 12 months-old APP-PS1 and WT mice for a total of 4 weeks using an anti-CD8 antibody treatment. While the treatment at this time of disease stage did neither affect the cognitive outcome nor plaque pathology, RNAseq analysis of the hippocampal transcriptome from APP-PS1 mice lacking CD8+ T-cells revealed highly altered neuronal- and synapse-related gene expression including an up-regulation for neuronal immediate early genes (IEGs) such as the Activity Regulated Cytoskeleton Associated Protein (Arc) and the Neuronal PAS Domain Protein 4 (Npas4). Gene ontology enrichment analysis illustrated that the biological processes “regulation of neuronal synaptic plasticity” and the cellular components “postsynapses” were over-represented upon CD8+ T-cell ablation. Additionally, Kegg pathway analysis showed up-regulated pathways for “calcium signaling”, “long-term potentiation”, “glutamatergic synapse” and “axon guidance”. Therefore, we conclude that CD8+ T-cells infiltrate the aged and AD brain and that brain CD8+ T-cells might directly contribute to neuronal dysfunction in modulating synaptic plasticity. Further analysis will be essential to uncover the exact mechanism of how CD8+ T-cells modulate the neuronal landscape and thereby contribute to AD pathology.
000154223 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000154223 588__ $$aDataset connected to CrossRef
000154223 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000154223 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000154223 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000154223 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000154223 650_2 $$2MeSH$$aAnimals
000154223 650_2 $$2MeSH$$aBrain: metabolism
000154223 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: metabolism
000154223 650_2 $$2MeSH$$aDisease Models, Animal
000154223 650_2 $$2MeSH$$aGene Expression
000154223 650_2 $$2MeSH$$aMice
000154223 650_2 $$2MeSH$$aMice, Transgenic
000154223 650_2 $$2MeSH$$aPresenilin-1: genetics
000154223 650_2 $$2MeSH$$aSynapses: metabolism
000154223 7001_ $$0P:(DE-HGF)0$$aLi, E.$$b1
000154223 7001_ $$aScharnagl, L.$$b2
000154223 7001_ $$aPoupardin, R.$$b3
000154223 7001_ $$aAltendorfer, B.$$b4
000154223 7001_ $$aMrowetz, H.$$b5
000154223 7001_ $$aHutter-Paier, B.$$b6
000154223 7001_ $$aWeiger, T. M.$$b7
000154223 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael$$b8$$udzne
000154223 7001_ $$aAttems, J.$$b9
000154223 7001_ $$0P:(DE-HGF)0$$aAigner, L.$$b10$$eCorresponding author
000154223 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2020.05.070$$gVol. 89, p. 67 - 86$$p67 - 86$$tBrain, behavior and immunity$$v89$$x0889-1591$$y2020
000154223 8564_ $$uhttps://www.sciencedirect.com/science/article/pii/S0889159119315739?via%3Dihub
000154223 8564_ $$uhttps://pub.dzne.de/record/154223/files/DZNE-2021-00084.pdf$$yOpenAccess
000154223 8564_ $$uhttps://pub.dzne.de/record/154223/files/DZNE-2021-00084.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000154223 909CO $$ooai:pub.dzne.de:154223$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000154223 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000008$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000154223 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000154223 9132_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000154223 9141_ $$y2020
000154223 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-28
000154223 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-01-28
000154223 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-28
000154223 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000154223 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000154223 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-25$$wger
000154223 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBRAIN BEHAV IMMUN : 2021$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-25
000154223 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bBRAIN BEHAV IMMUN : 2021$$d2022-11-25
000154223 9201_ $$0I:(DE-2719)1011303$$kAG Heneka 2$$lNeuroinflammation, Biomarker$$x0
000154223 980__ $$ajournal
000154223 980__ $$aVDB
000154223 980__ $$aUNRESTRICTED
000154223 980__ $$aI:(DE-2719)1011303
000154223 9801_ $$aFullTexts