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Anglada-Huguet M, Rodrigues S, Hochgräfe K, et al. Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice. Alzheimers Dement (N Y). 2021;7(1):e12170doi: 10.1002/trc2.12170.
Anglada-Huguet, M., Rodrigues, S., Hochgräfe, K., Mandelkow, E., & Mandelkow, E. M. (2021). Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice. Alzheimer's & dementia (New York, N. Y.), 7(1), e12170. https://doi.org/10.1002/trc2.12170
Anglada-Huguet, Marta, et al. "Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice." Alzheimer's & dementia (New York, N. Y.) vol. 7,1 (2021): e12170. doi: https://doi.org/10.1002/trc2.12170
Anglada-Huguet M, Rodrigues S, Hochgräfe K, Mandelkow E, Mandelkow EM. Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice. Alzheimers Dement (N Y). 2021 Jun 01;7(1):e12170. doi: 10.1002/trc2.12170. eCollection 2021. PMID: 34095439; PMCID: PMC8168941.
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Alzheimers Dement (N Y). 2021 Jun 01;7(1):e12170. doi: 10.1002/trc2.12170. eCollection 2021.

Inhibition of Tau aggregation with BSc3094 reduces Tau and decreases cognitive deficits in rTg4510 mice.

Alzheimer's & dementia (New York, N. Y.)

Marta Anglada-Huguet, Sara Rodrigues, Katja Hochgräfe, Eckhard Mandelkow, Eva-Maria Mandelkow

Affiliations

  1. German Center for Neurodegenerative Diseases DZNE Bonn Germany.
  2. Center for Advanced European Studies and Research CAESAR Bonn Germany.

PMID: 34095439 PMCID: PMC8168941 DOI: 10.1002/trc2.12170

Abstract

BACKGROUND: One of the major hallmarks of Alzheimer's disease (AD)is the aberrant modification and aggregation of the microtubule-associated protein Tau . The extent of Tau pathology correlates with cognitive decline, strongly implicating Tau in the pathogenesis of the disease. Because the inhibition of Tau aggregation may be a promising therapeutic target, we tested the efficacy of BSc3094, an inhibitor of Tau aggregation, in reducing Tau pathology and ameliorating the disease symptoms in transgenic mice.

METHODS: Mice expressing human Tau with the P301L mutation (line rTg4510) were infused with BSc3094 into the lateral ventricle using Alzet osmotic pumps connected to a cannula that was placed on the skull of the mice, thus bypassing the blood-brain barrier (BBB) . The drug treatment lasted for 2 months, and the effect of BSc3094 on cognition and on reversing hallmarks of Tau pathology was assessed.

RESULTS: BSc3094 significantly reduced the levels of Tau phosphorylation and sarkosyl-insoluble Tau. In addition, the drug improved cognition in different behavioral tasks and reduced anxiety-like behavior in the transgenic mice used in the study.

CONCLUSIONS: Our in vivo investigations demonstrated that BSc3094 is capable of partially reducing the pathological hallmarks typically observed in Tau transgenic mice, highlighting BSc3094 as a promising compound for a future therapeutic approach for AD.

© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

Keywords: Alzet pump; Alzheimer's disease; BSc3094; P301L Tau mutation; Tau pathology; aggregation inhibitor

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