The major defining pathological hallmarks of Alzheimer's disease (AD) are the 
accumulations of Aβ in senile plaques and hyperphosphorylated tau in 
neurofibrillary tangles and neuropil threads. Recent studies indicate that 
rather than these insoluble lesions, the soluble Aβ oligomers and 
hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological 
protein species are accompanied by cytoskeletal changes, mitochondrial 
dysfunction, Ca(2+) dysregulation, and oxidative stress. In this review, we 
discuss how the binding of Aβ to various integrins, defects in downstream focal 
adhesion signaling, and activation of cofilin can impact mitochondrial 
dysfunction, cytoskeletal changes, and tau pathology induced by Aβ oligomers. 
Such pathological consequences can also feedback to further activate cofilin to 
promote cofilin pathology. We also suggest that the mechanism of Aβ generation 
by the endocytosis of APP is mechanistically linked with perturbations in 
integrin-based focal adhesion signaling, as APP, LRP, and β-integrins are 
physically associated with each other.