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February 7, 2012
Tau Spreads On Its Own?
I've been meaning to mention the very interesting work that's shown up on tau protein in Alzheimer's. That's generally taken a back seat to amyloid in the protein-pathologies-of-Alzheimer's derby, but no one has been able to rule it out as a causative event, either. And the progress of tau pathology through the brain is quite suggestive - it tends to start in one region (the entorhinal cortex) and spread from there. The question is, what's driving that process? Is it tau itself spreading, or perhaps something inside the cell that causes tau problems is spreading, or is it some set of external conditions (that lead to tau pathologies) which is spreading?
This latest work goes a good way towards settling that question. (Here's one group's paper in PLoS One; the other paper in Neuron doesn't seem to be up yet, which has caused some controversy). The researchers in question engineered mice that express human tau protein localized to the entorhinal cortex (EC). They then sat back and watched what happened, taking sample along the way.
And what happened was a spectacular result. They found human tau in the EC initially, as expected. But over time, it began to show up in brain regions that are synaptically connected to the EC, and then it spread to the regions that are connected to those. This is human tau protein, remember - the only cells in the brains of these mice that should be able to make it are in the EC. In other words, the protein itself appears to be spreading from neuron to neuron, apparently through the synaptic junctions:
In general, our NT mouse model replicates the spatial and temporal aspects of the earliest stages (I–III) of Braak staging of tauopathy in Alzheimer's disease. We have demonstrated that tau pathology initiating in the EC can spread to other synaptically connected brain areas as the mice age, supporting the idea that AD progresses via an anatomical cascade as opposed to individual events occurring in differentially vulnerable regions.
They also now have a very interesting (and potentially very useful) mouse model of Alzheimer's pathology. There are still a huge number of open questions about Alzheimer's, don't get me wrong. But this is a real advance, in a field that doesn't see as many of those as everyone would like. Now to figure out how that protein is spreading (How's it excreted from the cell? How's it taken up by the next ones in line?) and why.
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