Claiming Confirmation of the Amyloid Hypothesis in Alzheimer's Disease

Most of the research community proceeds under the assumption that amyloid, deposits of misfolded proteins that form in tissues, is a causative agent in Alzheimer's disease. Amyloid levels rise with age, probably due to progressive failure of clearance mechanisms. Definitive proof of the role of amyloid has been slow in coming, however, for all that the weight of evidence is strong. From a biochemical point of view Alzheimer's is a very complex condition, and there has been plenty of room for alternate theories to flourish, especially given the slow progress towards meaningful treatments based on removing amyloid.

Researchers are here claiming confirmation of the amyloid hypothesis, which is news, though that might be overstating the case:

An innovative laboratory culture system has succeeded, for the first time, in reproducing the full course of events underlying the development of Alzheimer's disease. Using the system they developed, [investigators] now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease.

"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events - the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death. One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call 'Alzheimer's-in-a-dish,' we've been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death."

[The researchers] realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the [team] used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes - the amyloid precursor protein and - known to underlie early-onset familial Alzheimer's Disease (FAD).

After growing for six weeks, the FAD-variant cells were found to have significant increases in both the typical form of beta-amyloid and the toxic form associated with Alzheimer's. The variant cells also contained the neurofibrillary tangles that choke the inside of nerve cells causing cell death. Blocking steps known to be essential for the formation of amyloid plaques also prevented the formation of the tangles, confirming amyloid's role in initiating the process. The version of tau found in tangles is characterized by the presence of excess phosphate molecules, and when the team investigated possible ways of blocking tau production, they found that inhibiting the action of an enzyme called GSK3-beta - known to phosphorylate tau in human neurons - prevented the formation of tau aggregates and tangles even in the presence of abundant beta-amyloid and amyloid plaques.



While big pharma, etc...desperately look for a cure for alzheimers and the big profits therefrom...maybe the solution is already at hand? Simpler is better?

"Two trials using curcumin supplements rather than turmeric, however, failed to show a benefit. Curcumin is just one of hundreds of phytochemicals found in turmeric. Concentrated into pill form at up to 40 times the dose, no evidence of efficacy was found. Why didn't they get the same dramatic results we saw in the three case reports? Well, those three cases may have total flukes, but on the other hand turmeric, the whole food, is greater than the sum of its parts.
There is a long list of compounds that of been isolated from turmeric, and it's possible that each component in the mixture of curcumin-like compounds plays a distinct role in making it useful against Alzheimer's disease, and hence a mixture of compounds might better represent turmeric in its medicinal value better than curcumin alone. But why concoct some artificial mixture when Mother Nature already did it for us with turmeric? Because you can't patent the spice. And if you can't patent it, how are you going to charge more than 15 cents?"

Posted by: bob at October 22nd, 2014 5:33 AM

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