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Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer’s disease tau

dc.contributor.authorBrendel, Matthias
dc.contributor.authorDeussing, Maximilian
dc.contributor.authorBlume, Tanja
dc.contributor.authorKaiser, Lena
dc.contributor.authorProbst, Federico
dc.contributor.authorOverhoff, Felix
dc.contributor.authorPeters, Finn
dc.contributor.authorvon Ungern-Sternberg, Barbara
dc.contributor.authorRyazanov, Sergey
dc.contributor.authorLeonov, Andrei
dc.contributor.authorGriesinger, Christian
dc.contributor.authorZwergal, Andreas
dc.contributor.authorLevin, Johannes
dc.contributor.authorBartenstein, Peter
dc.contributor.authorYakushev, Igor
dc.contributor.authorCumming, Paul
dc.contributor.authorBoening, Guido
dc.contributor.authorZiegler, Sibylle
dc.contributor.authorHerms, Jochen
dc.contributor.authorGiese, Armin
dc.contributor.authorRominger, Axel
dc.date.accessioned2019-08-04T03:16:47Z
dc.date.available2019-08-04T03:16:47Z
dc.date.issued2019
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/16327
dc.description.abstractAbstract Background Augmenting the brain clearance of toxic oligomers with small molecule modulators constitutes a promising therapeutic concept against tau deposition. However, there has been no test of this concept in animal models of Alzheimer’s disease (AD) with initiation at a late disease stage. Thus, we aimed to investigate the effects of interventional late-stage Anle138b treatment, which previously indicated great potential to inhibit oligomer accumulation by binding of pathological aggregates, on the metabolic decline in transgenic mice with established tauopathy in a longitudinal 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) study. Methods Twelve transgenic mice expressing all six human tau isoforms (hTau) and ten controls were imaged by FDG-PET at baseline (14.5 months), followed by randomization into Anle138b treatment and vehicle groups for 3 months. FDG-PET was repeated after treatment for 3 months, and brains were analyzed by tau immunohistochemistry. Longitudinal changes of glucose metabolism were compared between study groups, and the end point tau load was correlated with individual FDG-PET findings. Results Tau pathology was significantly ameliorated by late-stage Anle138b treatment when compared to vehicle (frontal cortex − 53%, p < 0.001; hippocampus − 59%, p < 0.005). FDG-PET revealed a reversal of metabolic decline during Anle138b treatment, whereas the vehicle group showed ongoing deterioration. End point glucose metabolism in the brain of hTau mice had a strong correlation with tau deposition measured by immunohistochemistry (R = 0.92, p < 0.001). Conclusion Late-stage oligomer modulation effectively ameliorated tau pathology in hTau mice and rescued metabolic function. Molecular imaging by FDG-PET can serve for monitoring effects of Anle138b treatment.
dc.language.isoen
dc.publisherBioMed Central
dc.identifier.bibliographicCitationAlzheimer's Research & Therapy. 2019 Aug 01;11(1):67
dc.rightsopenAccess
dc.titleLate-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer’s disease tau
dc.typejournalArticle
dc.identifier.doi10.1186/s13195-019-0522-z
dc.type.versionpublishedVersion
dc.date.updated2019-08-04T03:16:47Z
dc.rights.holderThe Author(s).
dc.bibliographicCitation.volume11
dc.bibliographicCitation.issue1
dc.type.subtypejournalArticle
dc.bibliographicCitation.articlenumber67
dc.bibliographicCitation.journalAlzheimer's Research & Therapy


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