Aluminum and Alzheimer's disease: perspectives for a cytoskeletal mechanism.

Abstract

A considerable volume of literature has accumulated concerning the association of aluminum with Alzheimer's disease. The pathogenic mechanisms resulting in Alzheimer's disease remain unknown, but recent investigations have focused on cytoskeletal abnormalities as perhaps the key lesion in Alzheimer's disease and related neurological disorders. The diversity of neuronal functions that are dependent on cytoskeletal integrity suggests that subtle effects on polymerization, assembly, transcription, or processing of cytoskeletal elements may have significant and far-reaching neurological effects. That aluminum may participate in the development of neuropathological lesions characteristic of Alzheimer's disease is suggested by evidence that aluminum is a potent cytoskeletal toxin, produces cognitive deficits in laboratory animals, and can be detected within abnormal neurons isolated from brain tissue from Alzheimer's disease patients. In this review, a critical look will be taken at the enigmatic role aluminum has played in Alzheimer's disease research, the possibility of its pathogenicity, and its use as a tool for the investigation of cytoskeletal changes that may result in the biochemical and, ultimately, clinical manifestations of Alzheimer's disease.