neuropathological changes in the pdapp transgenic mouse model of alzheimer’s disease

alzheimer’s disease (ad) is a uniquely human disorder. although the pathogenesis of ad is not fully understood, growing evidence indicates that the deposition of beta-amyloid (aβ) and the local reactions of various cell types to this protein play major roles in the development of the disease. in the present study transgenic mice expressing mutant amyloid precursor protein (app) has been used. these mice exhibit selective neuronal death in the brain regions that are most affected in ad, suggesting that amyloid plaque formation is directly involved in ad neurons loss. brains from 12 transgenic animals and 12 age-matched non transgenic littermate controls (1 and 2 years old) were examined histopathologically. one year old transgenic animals (n=6) exhibit deposits of human aβ in the hippocampus, corpus callosum and cerebral cortex. by 2 years of age, a great number of diffuse and mature plaques were present in the cortex and hippocampus, and subcortical regions like thalamus and striatum. another major finding was reduction of cholinergic cells in the medial septum, striatum and diagonal band of broca. the present data are consistent with the hypothesis that the neuropathology begins in the cerebral cortex and hippocampus before spreading in a retrograde fashion to subcortical regions.