Neurobiology of Alzheimer's disease.

Although the specific process that destroys neurons in patients with Alzheimer's disease (AD) remains obscure, biochemical studies of AD neurohistologic lesions and molecular attempts to map and clone genes in familial AD have contributed greatly to our knowledge of AD. The major component of the extraneuronal neuritic plaque is beta-amyloid (A beta), which may be neurotoxic. The major component of the intraneuronal neurofibrillary tangle is hyperphosphorylated tau protein. It is unclear why this process damages the neuronal cytoskeleton Familial AD is genetically heterogeneous. Chromosomes 21, 14, and 1 are causative genes in early-onset familial AD. The apolipoprotein E4 allele of chromosome 19 is a risk factor for both early- and late-onset AD. Unraveling the actions of these three causative genes and the apolipoprotein E4 allele may explain disease mechanisms common to all patients with AD.