Deposition of Amyloid beta fibrils (fAbeta) plays a critical role in Alzheimer´s disease (AD).  FAbeta-induced dystrophy requires the activation of focal adhesion proteins and the formation of aberrant focal adghesion structures.  Focal adhesions are actin-based structures that provide a structural link between the extracellular matrix and the cytoskeleton.  To gain further insight in the molecular mechanism of neuronal degeneration in AD, here we explored the involvement of LIM kinase 1 (LIMK1), anad cofilin (Cofilin) in Abeta-induced dystrophy.  Cofilin is an actin binding protein that play a role in actin filament dynamics, and LIMK1 is the kinase that phosphorylates and thereby inhibits ADF/Cofilin.  Our data indicate that treatment of hippocampal neurons with fAbeta increases the level of phosphor-Cofilin and phosphor-LIMK1, accompanied by a dramatic remodeling of actin filaments and neuritic dystrophy.  A synthetic peptide, S3 peptide, which acts as a specific competitor for Cofilin phosphorylation by LIMK1, inhibited fAbeta-induced ADF/Cofilin phosphorylation, preventing dystrophy, indicating the involvement of LIMK1 in Abeta-induced neuronal degeneration in vitro.  Immunofluorescence analysis of APP23 and 3XTg-AD transgenic mice, and AD brain showed high level of P-LIMK1 in pathologically affected areas; and in neurons depicting early signs of AD-pathology.  Thus, LIMK1 activation may play a key role in the pathologic neuroplastic remodeling of neurites in AD