GSK3B and Alzheimer disease: Tideglusib, a thiadiazolinedione derivative (Fig. 14), is developed to irreversibly inhibit GSK3β without interaction with the ATP binding domain.145,146 In animal models of AD, it caused a reduction in neurofibrillary tangles and amyloid plaques with an improvement in memory.147,148 These data were confirmed by the preliminary data of a larger-scale phase II clinical trial in which tideglusib caused an improvement in cognitive functions along with a reduction in CSF β-secretase levels in a subgroup of mild AD patients.