Disease-modifying treatments for Alzheimer disease have focused mainly on reducing levels of amyloid-β in the brain. In this review, Giacobini and Gold stress that none of these efforts have produced clinically meaningful results. Importantly, amyloid deposition is not strongly correlated with cognition in multivariate analyses, unlike hyperphosphorylated tau, neurofibrillary tangles, and synaptic and neuronal loss, which are closely associated with memory deficits. They suggest that targeting tau pathology might be more clinically effective than amyloid-β-directed therapies. Immunization studies in animals indicate that reduction of intracellular levels of tau and phosphorylated tau is possible, and is associated with improved cognitive performance. In this paper, they present an analysis of the failure of amyloid-β-directed therapies, discuss limitations of the amyloid cascade hypothesis, and suggest the potential value of tau-targeted therapy for Alzheimer disease treatment.

Giacobini E and Gold G: Alzheimer disease therapy – moving from amyloid-β to tau. Nature Reviews Neurology [Epub ahead of print, November 12, 2013; doi:10.1038/nrneurol.2013.223]

http://www.nature.com/nrneurol/journal/vaop/ncurrent/abs/nrneurol.2013.223.html