New Alzheimer's Theory Links Amyloid Beta, Tau

Amyloid beta and tau proteins compete for the same binding sites on microtubules in neurons, suggesting that displacement of tau by amyloid beta, rather than aggregation of either protein, may be the primary driver of Alzheimer's disease pathology. Ryan R. Julian and colleagues used fluorescence polarization to measure the binding affinities of fluorescently labeled amyloid beta 1-40 and 1-42 to both individual tubulin proteins and microtubules. The authors found binding affinities comparable to those reported for tau. Sequence homology analysis across three alignment algorithms confirmed structural similarity between amyloid beta and the microtubule-binding domains of tau. Competitive binding experiments demonstrated that the introduction of recombinant human tau reduced, but did not eliminate, amyloid beta binding to microtubules, consistent with shared or overlapping binding sites. The authors' findings are supported by and help rationalize previous studies that had indirectly examined interactions between amyloid beta and microtubules. According to the authors, this microtubule nexus hypothesis reconciles longstanding contradictions between amyloid-centric and tau-centric models of Alzheimer's disease and suggests new therapeutic strategies targeting the competitive displacement of tau from microtubules.