The aberrant metabolism of tau and β-amyloid precursor protein (APP) has key roles in the neurodegenerative processes that contribute to the etiology of Alzheimer's disease (AD). These pathological characteristics of AD have recently been linked to the deregulation of cyclin-dependent kinase 5 (cdk5). The finding that the inducible expression of p25, which is the neurotoxic activator of cdk5, triggers progressive neurodegeneration and neurofibrillary tangle formation in mice provides compelling evidence that p25–cdk5 is one of the crucial pathways that can lead to AD pathophysiology. Furthermore, a role for cdk5 in modulating APP processing and β-amyloid generation is emerging. Therefore, as one of the molecular links between APP and tau, cdk5 might be a valuable target for therapeutic intervention in AD and other neurodegenerative diseases.