%0 Journal Article %J J Alzheimers Dis %D 2016 %T Reduction of Blood Amyloid-β Oligomers in Alzheimer's Disease Transgenic Mice by c-Abl Kinase Inhibition. %A Estrada, Lisbell D %A Chamorro, David %A Yañez, María José %A Gonzalez, Marcelo %A Leal, Nancy %A von Bernhardi, Rommy %A Dulcey, Andrés E %A Marugan, Juan %A Ferrer, Marc %A Soto, Claudio %A Zanlungo, Silvana %A Inestrosa, Nibaldo C %A Alvarez, Alejandra R %X

One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of amyloid plaques, which are deposits of misfolded and aggregated amyloid-beta peptide (Aβ). The role of the c-Abl tyrosine kinase in Aβ-mediated neurodegeneration has been previously reported. Here, we investigated the therapeutic potential of inhibiting c-Abl using imatinib. We developed a novel method, based on a technique used to detect prions (PMCA), to measure minute amounts of misfolded-Aβ in the blood of AD transgenic mice. We found that imatinib reduces Aβ-oligomers in plasma, which correlates with a reduction of AD brain features such as plaques and oligomers accumulation, neuroinflammation, and cognitive deficits. Cells exposed to imatinib and c-Abl KO mice display decreased levels of β-CTF fragments, suggesting that an altered processing of the amyloid-beta protein precursor is the most probable mechanism behind imatinib effects. Our findings support the role of c-Abl in Aβ accumulation and AD, and propose AD-PMCA as a new tool to evaluate AD progression and screening for drug candidates.

%B J Alzheimers Dis %V 54 %P 1193-1205 %8 2016 Oct 04 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27567806?dopt=Abstract %R 10.3233/JAD-151087