Altered subcellular distribution of c-Abl in Alzheimer's disease.
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-beta-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 Abeta signal transduction and generation of tau pathology in AD.
Department of Pathology, University of Pittsburgh, School of Medicine, BST S-420, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Zheng
Z
Jing
John
J
Caltagarone
Robert
R
Bowser
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D000704:Analysis of Variance; D016022:Case-Control Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D000682:Amyloid; D016900:Neurofilament Proteins; D016875:tau Proteins; C051774:neurofilament protein H; D013912:Threonine; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl