Neurotoxic effects of aluminum (Al) were recognized >100 years ago, bu
t have only recently been studied in detail. By far, the most dramatic
effect of Al is that of producing intraneuronal perikaryal neurofilam
entous aggregates, which consist of phosphorylated neurofilaments. Sev
eral species have been used to demonstrate this effect, rabbit being m
ost common; the effect also is seen in in vitro systems. Besides its r
ole in producing neurofibrillary pathology, Al appears to modify the b
lood-brain barrier and exert cholinergic and noradrenergic effects. Po
ssible mechanisms of Al neurotoxicity could be related to cell damage
via free radical production, impairment of glucose metabolism, and eff
ects on signal transduction.