During a recent clinical and neuropathologic evaluation of a large population of brains collected at autopsy, attention was drawn to a subset of Alzheimer's disease (AD) patients presenting with prominent visual symptomatology as the first sign of the disease. In this population, a shift in the distribution of pathologic profiles had occurred such that the primary visual areas and the visual association areas had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathologic hallmarks of the disease, neurofibrillary tangles and neuritic plaques. Furthermore, the distribution of pathologic lesions in the AD cases with visual symptomatology revealed the disruption of specific visual association pathways, which are normally affected to a lesser degree in AD. These data suggest that in some cases of AD, the particular psychologic and neurologic symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected by a differential distribution of the neuropathologic markers of the disease.