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- Titel:
Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau.
- Dokumenttyp:
- Journal Article
- Autor(en):
- Brendel, Matthias; Deussing, Maximilian; Blume, Tanja; Kaiser, Lena; Probst, Federico; Overhoff, Felix; Peters, Finn; von Ungern-Sternberg, Barbara; Ryazanov, Sergey; Leonov, Andrei; Griesinger, Christian; Zwergal, Andreas; Levin, Johannes; Bartenstein, Peter; Yakushev, Igor; Cumming, Paul; Boening, Guido; Ziegler, Sibylle; Herms, Jochen; Giese, Armin; Rominger, Axel
- Abstract:
- 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.
- Zeitschriftentitel:
- Alzheimers Res Ther
- Jahr:
- 2019
- Band / Volume:
- 11
- Heft / Issue:
- 1
- Volltext / DOI:
- doi:10.1186/s13195-019-0522-z
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/31370885
- TUM Einrichtung:
- Klinik und Poliklinik für Nuklearmedizin
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