In a study just published on Dec 9th in the Journal Science, researchers Kwasi Mawuenyega et al led by Dr. Randall Bateman MD demonstrated that it is perhaps the impaired clearance of Beta-Amyloid Proteins in the brain and not their overproduction that potentially leads to Alzheimer’s Disease. This is a SIGNIFICANT research finding because the predominant view in the Alzheimer’s research community has been that patients with Alzheimer’s Disease over produce this beta-amyloid protein (the so called Amyloid hypothesis of Alzheimer’s).
The idea for this line of thinking came to Dr. Randall Bateman MD when he was a Neurology resident doctor at the Washington University in St. Louis in 2003. Over lunch in the cafeteria (as reported in the NY Times) he wondered with neurologist Dr. David Holtzman if the beta amyloid build up in patients’ brains was because people making too much or because they were unable to dispose of what they made?
Dr. Randall Bateman and Dr. David Holtzman of Washington University St. Louis
And after seven years of research, including being turned down by the NIH to fund his study to test this hypothesis, his team has been able to demonstrate that it is indeed the case that Alzheimer’s patients have an impaired clearance of beta-amyloid. They demonstrated this in a clinical study in which Dr. Bateman was the first study subject himself, tapping into this spinal cord fluid to measure the clearance of a tagged amino acid that is required for beta-amyloid synthesis. The key findings was that normally 50% of the beta amyloid is cleared within 8 hrs but its clearance maybe impaired by 30% or so in Alzheimer’s disease patients.
This discovery opens up the possibility of developing drugs to improve the clearance rates as opposed to looking at ways to stop/reduce amyloid production, which has been shown to fail in recent sudies (Eli Lily’s recent clinical trial was stopped because the drug being tested drastically reduced amyloid function resulting in undesirable adverse effects).
What is particularly exciting is that such big breakthroughs are usually based on simple questions that seem to an obvious line of reasoning retrospectively. Though its too early to say anything, this one discovery could drastically alter how new research is done in finding cures for Alzheimer. Such studies and original thinkers are needed to keep the ever expand the envelope of scientific discovery and dogged determination to arrive at an answer. Kudos to Dr. Randall Bateman and team.
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