There always seems to be something new emerging in Alzheimer's disease research. In the last few years, at least one widely accepted hypothesis, the amyloid hypothesis, has come under scrutiny. In AD, it was thought that peptides aggregate into beta-amyloid fibrils (Aß) which causes toxicity to neurons.
However, many reports in the last two years are suggesting that it's not the aggregated beta-amyloid, but its soluble precursors that seem to be more toxic. There were some indications that this was true before too. For example, neuronal damage and memory impairment did not always correlate with Aß levels.
Another big hypothesis that has been widely prevelant in the AD community is that metals such as copper, aluminium, iron, and zinc, might correlate with Aß aggregation. New reports also suggest that these metals may in fact bind to the soluble and toxic forms of Aß, and help them to aggregate. One very interesting aspect of metabolism emerging from this research seems to be that it's not necessarily a larger amount of these metals from our environment or diet that's causing the problems, but an age-related breakdown in metal metabolism in the brain, which is an especially capacious reservoir of metals. Thus, perhaps we need not be especially worried about getting more copper or zinc from our diets.
One more thing that the metals might be doing is to help in free-radical generation, that might damage neurons. Again, there is still a correlation vs causation problem with this hypothesis, but free radicals are being increasingly found in vitro, when metals are added to Aß fibrils. While aluminium seems to have been largely a scare idea, zinc and copper are emerging as more plausible agents for free radical production and neuronal damage.
Based on evolutionary concepts, I cannot help but think that there may actually have been some protective function of amyloid in ancient human civilizations. Maybe it sequestered copper and provided a ready source when there was a lack of copper (or iron for that matter) in the diet. Or maybe it recruited copper to fight microorganisms and especially bacteria, at a time when there were no defenses against them except for natural ones. In this way, it could have dealt a double blow; denying essentials metals to the bacteria, and recruiting them to produce free radicals which would kill the little beasties.
In any case, AD research at the molecular level seems to be advancing rapidly, and we can expect some interesting discoveries in the years to follow.
1. A nice review on AD and amyloid, free radicals, and oxidative damage
2. A recent Angewandte Chemie paper on the influence of copper concentrations on Aß geometry, morphology, and aggregation.
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