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At present it has been known that the amyloid toxicity was dissociated from the cognitive impairment, that is, Alzheimer's treatment in amyloid toxicity was not consisted between mice and human experiment. Amyloid treatment induced the cognitive recovery in mice, but in human case, the same recovery could not be observed. In ICAD congress 2009, one report has attracted many attentions of scientist. The drug dimebon was approved to cure the cognitive impairment of Alzheimer's patient, which has been reported to increase beta-amyloid protein in Alzheimer's model mice. This unexpected result shows an inconsistent result between human and mice case. Why was the inconsistent result observed between human and mice case?
We recently have observed the big difference of urinary excretion of homocysteic acid (HA) between human and mice. Here is main result. Comparison of urinary HA level between human and mice
Human (male): 34 .8 + 8.1 m moles/70 kg body weight/day (n=7)
Mice (male): 25.1+ 5.0 n moles/40 g body weight/day (n=5)
[29.3 + 5.8 μmoles/70kg body weight/day]
Human/mice = 1187
Human: Male Down syndrome (36.1 + 5.3 years old)
Mice: Male 3xTg-AD mice (12 month old)
What do you think about this result? The result is simply compared at same body weight between human and mice. This method is not adequated to compare them, but urinary excretion of HA is easy compared between them. Now human excreted HA more than 1000 times higher than that of mice.This observation suggests that human is more severe for HA toxicity than mice. In other words, human pathogenic mechansim is quite different from that of mice.
Now it is easy understood that Alzheimer's pathogenic mechanism seems to be different between human and mice case, then we should pay attention to use the model mice for the study of Alzheimer's pathogenic mechanism carefully.
Additional cited evidence: Gandy et al 2009. Dimebon®, A Clinically Promising Drug For Alzheimer Disease, Regulates Amyloid-Beta Metabolism In Cultured Cells, In Isolated Nerve Terminals, And In The Interstitial Fluid Of The Living Rodent Brain. Jul 15, 2009 ICAD 2009. S4-04-06