Senile plaques (SP) and neurofibrillary tangles (NFT) are the major histopathological changes that occur in Alzheimer's disease (AD). How these two different types of lesions are related to each other and to the dementia of AD is unknown. Recent studies lead to paradoxical conclusions: NFT and neuronal alterations such as synapse loss are much more closely related to the symptoms of dementia than are SP. However, mutations in the beta-amyloid protein of SP have been found in some patients with familial AD, suggesting that an abnormality in amyloid causes the development of SP, NFT and AD dementia. Examination of transgenic animals that produce amyloid precursor protein (APP), or altered forms of APP, may lead to the development of an animal model of AD, and ultimately to answers that link amyloid production to neuronal alterations, and cognitive impairments.