The neurobiology of Alzheimer's disease

The defining histological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and neuritic plaques, although neither is pathognomonic for this disorder. The distribution of AD histopathology suggests selective neuronal vulnerability, with specific cell populations affected within discrete regions of the cerebral hemispheres and within certain subcortical and brain-stem nuclear areas. At the ultrastructural level, tangles and plaque neurites contain paired helical filaments whose composition is unknown but may include altered cytoskeletal elements. Amyloid, deposited in plaque cores and often focally present within the cerebral vasculature, contains a polypeptide ("beta-protein," or "beta-amyloid") encoded by a chromosome 21 gene. At least in occasional families, AD has been linked to a separate chromosome 21 locus, but different underlying genetic factors may operate in other cases. Inorganic substances, including aluminum and silicon, are reported to co-localize within tangle-bearing neurons and plaque cores. Specific environmental agents have not been confirmed to be pathogenetically important, however, but may eventually prove to exert a permissive, facilitatory, or even causative role in many AD patients.