PHYSICAL DAMAGE TO RAT CORTICAL AXONS MIMICS EARLY ALZHEIMERS NEURONAL PATHOLOGY

WE investigated the reactive cytoskeletal changes following physical d amage to axons in the rodent neocortex and compared these with the ear liest 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 o f neurofilaments, Morphologically and neurochemically identical abnorm al axons were present within neocortical beta-amyloid deposits of indi viduals in the early stages of AD. Physically damaged rat cortical axo ns may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid dep osition may physically damage local axons, with further neurofibrillar y changes due to the reactive neuronal response to this type of injury .