The role of beta-amyloid in Alzheimer's disease.

Alzheimer's disease pathology Alzheimer's disease (AD) is characterized, upon postmortem analyses of the brain, by the presence of two major pathologic lesions, the senile or neu- ritic plaque, and neurofibrillary tangles, both identified by Alois Alzheimer in 1906. Neuritic plaques are composed of extracellular fibrillar deposits of the beta-amyloid peptide, Ab, and are often associated with dystrophic neu- rites, activated microglial cells, and activated astrocytes. They are found widely in the limbic and association areas of the temporal cortex, as well as in the hippocampus, a structure that is affected dramatically in the disease (1). Neurofibrillary tangles, or NFTs, which have been shown to be com- posed of the abnormally phosphorylated microtubule-associated protein tau (2), are found extensively in all of the brain areas affected in AD. They occur as intraneuronal, cytoplasmic inclusions, ultrastructurally shown to occur as interwound paired-helical filaments (PHF), remarkably resistant to solubili- zation even in strong chaotropic agents. Although both of these prominent pathologic lesions often occur simultaneously in the majority of AD cases, NFTs are sometimes found in diseases other than AD, especially some of the ''taupathies'' without coincidental beta-amyloid plaques. But all cases of clinical AD that have been analyzed for neuropathology have been shown to have Ab deposits, although the nature and extent of these varies widely in both sporadic and familial forms of the disease.