000258261 001__ 258261
000258261 005__ 20240826165951.0
000258261 0247_ $$2doi$$a10.3390/ijms24119260
000258261 0247_ $$2pmid$$apmid:37298211
000258261 0247_ $$2pmc$$apmc:PMC10252552
000258261 0247_ $$2ISSN$$a1422-0067
000258261 0247_ $$2ISSN$$a1661-6596
000258261 0247_ $$2altmetric$$aaltmetric:149868895
000258261 037__ $$aDZNE-2023-00607
000258261 041__ $$aEnglish
000258261 082__ $$a540
000258261 1001_ $$0P:(DE-2719)9000008$$aAnglada-Huguet, Marta$$b0$$eFirst author$$udzne
000258261 245__ $$aReversal of Tau-Dependent Cognitive Decay by Blocking Adenosine A1 Receptors: Comparison of Transgenic Mouse Models with Different Levels of Tauopathy.
000258261 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2023
000258261 3367_ $$2DRIVER$$aarticle
000258261 3367_ $$2DataCite$$aOutput Types/Journal article
000258261 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1686819141_19488
000258261 3367_ $$2BibTeX$$aARTICLE
000258261 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000258261 3367_ $$00$$2EndNote$$aJournal Article
000258261 520__ $$aThe accumulation of tau is a hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A1 receptor antagonist rolofylline (KW-3902) has previously been shown to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mouse line expressing full-length pro-aggregant tau (TauΔK) at low levels, with late onset of disease. However, the efficacy of treatment remained to be explored for cases of more aggressive tauopathy. Using a combination of behavioral assays, imaging with several PET-tracers, and analysis of brain tissue, we compared the curative reversal of tau pathology by blocking adenosine A1 receptors in three mouse models expressing different types and levels of tau and tau mutants. We show through positron emission tomography using the tracer [18F]CPFPX (a selective A1 receptor ligand) that intravenous injection of rolofylline effectively blocks A1 receptors in the brain. Moreover, when administered to TauΔK mice, rolofylline can reverse tau pathology and synaptic decay. The beneficial effects are also observed in a line with more aggressive tau pathology, expressing the amyloidogenic repeat domain of tau (TauRDΔK) with higher aggregation propensity. Both models develop a progressive tau pathology with missorting, phosphorylation, accumulation of tau, loss of synapses, and cognitive decline. TauRDΔK causes pronounced neurofibrillary tangle assembly concomitant with neuronal death, whereas TauΔK accumulates only to tau pretangles without overt neuronal loss. A third model tested, the rTg4510 line, has a high expression of mutant TauP301L and hence a very aggressive phenotype starting at ~3 months of age. This line failed to reverse pathology upon rolofylline treatment, consistent with a higher accumulation of tau-specific PET tracers and inflammation. In conclusion, blocking adenosine A1 receptors by rolofylline can reverse pathology if the pathological potential of tau remains below a threshold value that depends on concentration and aggregation propensity.
000258261 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000258261 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x1
000258261 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000258261 650_2 $$2MeSH$$aMice
000258261 650_2 $$2MeSH$$aAnimals
000258261 650_2 $$2MeSH$$aMice, Transgenic
000258261 650_2 $$2MeSH$$aReceptor, Adenosine A1: genetics
000258261 650_2 $$2MeSH$$aReceptor, Adenosine A1: metabolism
000258261 650_2 $$2MeSH$$atau Proteins: genetics
000258261 650_2 $$2MeSH$$atau Proteins: metabolism
000258261 650_2 $$2MeSH$$aHippocampus: metabolism
000258261 650_2 $$2MeSH$$aTauopathies: drug therapy
000258261 650_2 $$2MeSH$$aTauopathies: genetics
000258261 650_2 $$2MeSH$$aTauopathies: metabolism
000258261 650_2 $$2MeSH$$aCognition
000258261 650_2 $$2MeSH$$aDisease Models, Animal
000258261 650_7 $$2Other$$aAlzheimer’s disease
000258261 650_7 $$2Other$$aAlzheimer’s disease
000258261 650_7 $$2Other$$aAlzheimer’s disease
000258261 650_7 $$2Other$$aAlzheimer’s disease
000258261 650_7 $$2Other$$aPET
000258261 650_7 $$2Other$$aadenosine A1 receptor
000258261 650_7 $$2Other$$abehavior
000258261 650_7 $$2Other$$arolofylline
000258261 650_7 $$2Other$$asynapses
000258261 650_7 $$2Other$$atau protein
000258261 650_7 $$2NLM Chemicals$$aReceptor, Adenosine A1
000258261 650_7 $$2NLM Chemicals$$atau Proteins
000258261 7001_ $$00000-0002-6166-4818$$aEndepols, Heike$$b1
000258261 7001_ $$0P:(DE-2719)2810788$$aSydow, Astrid$$b2$$udzne
000258261 7001_ $$0P:(DE-2719)2812522$$aHilgers, Ronja$$b3$$udzne
000258261 7001_ $$aNeumaier, Bernd$$b4
000258261 7001_ $$0P:(DE-2719)2811239$$aDrzezga, Alexander$$b5$$udzne
000258261 7001_ $$0P:(DE-2719)2812350$$aKaniyappan, Senthilvelrajan$$b6$$udzne
000258261 7001_ $$0P:(DE-2719)2541671$$aMandelkow, Eckhard$$b7$$udzne
000258261 7001_ $$0P:(DE-2719)2541658$$aMandelkow, Eva-Maria$$b8$$eLast author$$udzne
000258261 770__ $$aTransgenic Mice in Human Diseases: Insights from Molecular Research 4.0
000258261 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms24119260$$gVol. 24, no. 11, p. 9260 -$$n11$$p9260$$tInternational journal of molecular sciences$$v24$$x1422-0067$$y2023
000258261 8564_ $$uhttps://www.mdpi.com/1422-0067/24/11/9260
000258261 8564_ $$uhttps://pub.dzne.de/record/258261/files/DZNE-2023-00607%20SUP.zip
000258261 8564_ $$uhttps://pub.dzne.de/record/258261/files/DZNE-2023-00607.pdf$$yOpenAccess
000258261 8564_ $$uhttps://pub.dzne.de/record/258261/files/DZNE-2023-00607.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000258261 909CO $$ooai:pub.dzne.de:258261$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000008$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810788$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812522$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811239$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812350$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b6$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2541671$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b7$$kDZNE
000258261 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2541658$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000258261 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000258261 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x1
000258261 9141_ $$y2023
000258261 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-25
000258261 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000258261 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-25
000258261 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2022-11-25
000258261 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000258261 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2022-11-25
000258261 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J MOL SCI : 2022$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-07-07T16:31:47Z
000258261 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-07-07T16:31:47Z
000258261 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-07-07T16:31:47Z
000258261 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-25
000258261 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bINT J MOL SCI : 2022$$d2023-08-25
000258261 9201_ $$0I:(DE-2719)1013015$$kAG Mandelkow 2 ; AG Mandelkow 2$$lCell and Animal Models of Neurodegeneration$$x0
000258261 9201_ $$0I:(DE-2719)1013014$$kAG Mandelkow 1 ; AG Mandelkow 1$$lStructural Principles of Neurodegeneration$$x1
000258261 9201_ $$0I:(DE-2719)1011305$$kAG Schneider$$lTranslational Dementia Research (Bonn)$$x2
000258261 9201_ $$0I:(DE-2719)1011202$$kAG Boecker$$lPositron Emissions Tomography (PET)$$x3
000258261 980__ $$ajournal
000258261 980__ $$aVDB
000258261 980__ $$aUNRESTRICTED
000258261 980__ $$aI:(DE-2719)1013015
000258261 980__ $$aI:(DE-2719)1013014
000258261 980__ $$aI:(DE-2719)1011305
000258261 980__ $$aI:(DE-2719)1011202
000258261 9801_ $$aFullTexts