Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease

C. M. Wischik*, J. M D Storey, D. J. Wischik, C. R. Harrington

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Tau pathology in Alzheimer's disease (AD) initiates early, before clinical symptoms are observed and before accumulation of extracellular amyloid-β. Tau aggregation is an autocatalytic process that does not depend on its phosphorylation and is highly correlated with clinical dementia. Tau aggregation inhibitors (TAIs) could provide the therapeutic means for treating AD. We have developed cell-free and cellular models and transgenic mice that model tauopathy and demonstrate the molecular basis for achieving pharmacological selectivity of TAIs. Methylthioninium chloride, the first selective TAI identified, has demonstrated efficacy in a phase 2 trial of AD on both clinical and functional molecular neuroimaging end points. This supports the potential for use of TAIs both for prevention and for treatment of the disease. Leucomethylthioninium is now in phase 3 trials of AD and behavioral-variant frontotemporal degeneration in order to confirm the concept of TAI therapy for these tauopathies.

Original languageEnglish
Title of host publicationDeveloping Therapeutics for Alzheimer's Disease
Subtitle of host publicationProgress and Challenges
EditorsMichael S. Wolfe
PublisherElsevier Inc.
Pages385-436
Number of pages52
ISBN (Electronic)9780128021644
ISBN (Print)9780128021736
DOIs
Publication statusPublished - 15 Jun 2016

Fingerprint

Tauopathies
Alzheimer Disease
Functional Neuroimaging
Methylene Blue
Amyloid
Transgenic Mice
Dementia
Phosphorylation
Pharmacology
Pathology
Therapeutics
Inhibition (Psychology)
Alzheimer disease, familial, type 3
Alzheimer disease type 2

Keywords

  • Alzheimer's disease
  • Clinical trials
  • LMTX
  • Methylthioninium
  • Tau aggregation inhibitors
  • Tau protein
  • Tauopathy

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Wischik, C. M., Storey, J. M. D., Wischik, D. J., & Harrington, C. R. (2016). Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease. In M. S. Wolfe (Ed.), Developing Therapeutics for Alzheimer's Disease: Progress and Challenges (pp. 385-436). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-802173-6.00015-0

Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease. / Wischik, C. M.; Storey, J. M D; Wischik, D. J.; Harrington, C. R.

Developing Therapeutics for Alzheimer's Disease: Progress and Challenges. ed. / Michael S. Wolfe. Elsevier Inc., 2016. p. 385-436.

Research output: Chapter in Book/Report/Conference proceedingChapter

Wischik, CM, Storey, JMD, Wischik, DJ & Harrington, CR 2016, Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease. in MS Wolfe (ed.), Developing Therapeutics for Alzheimer's Disease: Progress and Challenges. Elsevier Inc., pp. 385-436. https://doi.org/10.1016/B978-0-12-802173-6.00015-0
Wischik CM, Storey JMD, Wischik DJ, Harrington CR. Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease. In Wolfe MS, editor, Developing Therapeutics for Alzheimer's Disease: Progress and Challenges. Elsevier Inc. 2016. p. 385-436 https://doi.org/10.1016/B978-0-12-802173-6.00015-0
Wischik, C. M. ; Storey, J. M D ; Wischik, D. J. ; Harrington, C. R. / Inhibition of Tau Aggregation as a Basis for Treatment and Prevention of Alzheimer's Disease. Developing Therapeutics for Alzheimer's Disease: Progress and Challenges. editor / Michael S. Wolfe. Elsevier Inc., 2016. pp. 385-436
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