Aluminum intoxication and the victim of Alzheimer's disease: similarities and differences.
Aluminum (Al) has been implicated in the pathogenesis and may produce a model of senile dementia of the Alzheimer's type (SDAT). To better understand the effects of Al on the mammalian brain, Al was studied in rabbits and rats using several experimental approaches. Similar behavioral toxicity and site and degree of neurofibrillary tangle (NFT) development were obtained after intracerebroventricular (icv) or repeated sc Al, although a more protracted time course after the latter. SDAT victims demonstrate some similar behavioral signs but a different type of NFT. A classically conditioned, defensive reflex (nictitating membrane extension) was used to compare response acquisition, retention, and extinction in Al-exposed and control rabbits of various ages. Both increasing age and Al exposure attenuated these measures, suggesting that advanced age and Al intoxication provide behavioral models of SDAT. A deficit in acquisition of a classically conditioned response (eyeblink) in senile-demented patients has been reported. These cognitive deficits in rabbits occurred after a less than two-fold increase in brain Al. Brain Al in SDAT victims has been reported to be unchanged or slightly increased. Further similarity to SDAT was obtained with 4-aminopyridine (4-AP) which attenuated Al-induced behavioral deficits in rabbits and the Al inhibition of glutamate release from rat hippocampal slices. 4-Aminopyridine has been reported to attenuate behavioral deficits in SDAT patients. A tubulin, GTP binding site was blocked in SDAT victim brain but not in control or Al-intoxicated rabbit brain, indicating a biochemical dissimilarity. In summary, Al-intoxication produces a model of SDAT with many similarities but significant differences.
Yokel
R A
RA
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Provan
S D
SD
Meyer
J J
JJ
Campbell
S R
SR
D000535:Aluminum / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D011817:Rabbits
D000535:Aluminum