We investigated the reactive cytoskeletal changes following physical damage to axons in the rodent neocortex and compared these with the earliest neuronal alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into the rodent somatosensory cortex resulted in ring- and club-like axonal changes characterized by an accumulation of neurofilaments. Morphologically and neurochemically identical abnormal axons were present within neocortical beta-amyloid deposits of individuals in the early stages of AD. Physically damaged rat cortical axons may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may physically damage local axons, with further neurofibrillary changes due to the reactive neuronal response to this type of injury.