Minocycline reduces the development of abnormal tau species in models of Alzheimer's disease

 Minocycline, a tetracycline derivative, has potent antiinflammatory, antiapoptotic, and neuroprotective effects in several models of neurodegenerative disease, including models of AD with amyloid pathology. This study aims at investigating the neuroprotective effects of minocycline in the htau transgenic model of tauopathy.  The authors found that minocycline reduced Aβ-induced neuronal death in primary neuronal cultures and that this is associated with reduced caspase-3 activation and caspase-3-mediated tau cleavage. Treatment of 2 groups ( young: 3-4 months; old; 12 months) of htau mice with minocycline resulted in inhibition of insoluble tau aggregate levels and tau phosphorylation. Minocycline reduced tau phosphorylation and aggregation in young  htau mice but only reduced tau aggregate load, in old htau mice.The reduction in tau pathology correlates with caspase-3 inhibition and reduced caspase-3 cleavage of tau. Importantly, minocycline reduced the amount of abnormal tau species in both young and aged mice. These results suggest that minocycline may have therapeutic benefit for the treatment of AD and related tauopathies.