The localization of alpha 4 integrin subunit and of fibronectin in Alzheimer's disease (AD), Down's syndrome, Lewy body dementia (DLB) and normal brains was immunohistochemically investigated. Antibodies against the alpha 4 subunit and a fibronectin specific antibody stained 'neuritic' plaques in AD and Down's syndrome, while 'preamyloid' and 'burned-out' plaques remained negative. No alpha 4 integrin subunit or fibronectin immunoreactivity was detected in the plaques of DLB consistent with the absence of neuritic plaques. In addition, hippocampal pyramidal neurons and some neocortical neurons showed immunoreactivity with alpha 4 subunit and fibronectin antibodies in all aged individuals, but not in younger controls. These results suggest an age-related and localized expression of alpha 4 integrin subunit and fibronectin in the brain.