The Pathobiology of Cofilin in Alzheimer Disease

James Bamburg, Colorado State University

September 9, 2009 @ 05:00 pm to 06:00 pm

108 Wartik Laboratory, CG623 Hershey

Event Website

Brains from human AD patients contain tandem arrays of cofilin immunostaining that appear to be identical to cofilin-actin rods, which can be induced to form in neurites of dissociated hippocampal neurons exposed to a variety of degenerative stimuli. Isolated rods contain cofilin-actin in a 1:1 complex. Multiple signaling pathways have been identified that mediate cofilin activation leading to rod formation. Rods entrap mitochondria and vesicles which explain their inhibitory effects on transport that contribute to distal neurite degeneration. Ab-induced rods are elevated significantly within the dentate gyrus and mossy fiber (hilus) region and are reversible following washout of Ab peptide, suggesting that they may mediate the transient effects on memory and learning observed upon single infusions of Ab into adult rat brain. Cofilin-actin rods sequester specific phosphorylated forms of tau, suggesting a relationship between the two that give rise to striated neuropil threads, a common feature of AD brain. Taken together, our data suggest that cofilin-actin rods play a major role in the development of AD pathology.

Contact

Gong Chen
guc2@psu.edu