Affiliations: [a] Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA | [b] Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA | [c] Pittsburgh Institute for Neurodegeneration, University of Pittsburgh, Pittsburgh, PA, USA
Correspondence:
[*]
Corresponding author: Robert Bowser, PhD, Department of Pathology, University of Pittsburgh, School of Medicine, BST S-420, 200 Lothrop Street, Pittsburgh, PA 15261, USA. Tel.: +1 412 383 7819; Fax: +1 412 648 1916; E-mail: Bowserrp@upmc.edu.
Abstract: c-Abl is a non-receptor tyrosine kinase that participates in multiple signaling pathways linking the cell surface, cytoskeleton, and the nucleus. Recent in vitro studies have also linked c-Abl to amyloid-β-induced toxicity and tau phosphorylation. To further characterize a potential role of c-Abl in Alzheimer's disease (AD), we examined the expression and distribution of total and phosphorylated forms of c-Abl in the hippocampus of AD and control subjects. Laser scanning confocal microscopy was used to examine the colocalization of c-Abl with AD pathology. Our results demonstrate alterations in the presence and distribution of c-Abl and phosphorylated isoforms of c-Abl within the hippocampus during AD. Total unphosphorylated c-Abl was highest in non-demented control hippocampus. Activated isoforms of c-Abl were most abundant in AD hippocampus and co-localized with AD pathology, including granulovacuolar degeneration bodies. c-Abl interacts with phosphorylated tau in AD brain and may contribute to the formation of tau pathology. These studies demonstrate altered activation and distribution of c-Abl during AD, suggesting a role for c-Abl in Aβ signal transduction and generation of tau pathology in AD.
Keywords: Alzheimer's disease, amyloid-β, c-Abl, granulovacuolar degeneration bodies, tau
