Therapeutic strategies for tau mediated neurodegeneration

Based on the amyloid hypothesis, controlling beta-amyloid protein (A beta) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, A beta removal or reducing A beta production has shown limited efficacy. Moreover, while active immunisation with A beta resulted in the clearance of A beta, it did not prevent tau pathology or neurodegeneration. This prompts the concern that it might be too late to employ A beta targeting therapies once tau mediated neurodegeneration has occurred. Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration.