Title | Reduction of Blood Amyloid-β Oligomers in Alzheimer's Disease Transgenic Mice by c-Abl Kinase Inhibition. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Estrada, LD, Chamorro, D, Yañez, MJosé, Gonzalez, M, Leal, N, von Bernhardi, R, Dulcey, AE, Marugan, J, Ferrer, M, Soto, C, Zanlungo, S, Inestrosa, NC, Alvarez, AR |
Journal | J Alzheimers Dis |
Volume | 54 |
Issue | 3 |
Pagination | 1193-1205 |
Date Published | 2016 Oct 04 |
ISSN | 1875-8908 |
Abstract | 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. |
DOI | 10.3233/JAD-151087 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 27567806 |