Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein.

ABSTRACT: The mechanistic relationship between amyloid ?1-42 (A?1-42) and the alteration of Tau protein are debated. We investigated the effect of A?1-42 monomers and oligomers on Tau, using mice expressing wild-type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of A?1-42, mice were sacrificed after 3 h or 4 days. The short-lasting treatment with A? monomers, but not oligomers, showed a conformational PHF-like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. A? monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. A? oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that A?1-42 monomers foster synaptic activity. Our results suggest that A? monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti-A? therapies should be targeted to A?1-42 monomers too.

SUBMITTER: Manassero G 

PROVIDER: S-EPMC5013016 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature