This is an “oh, sh..” moment for many a researcher. It seems that the premise of much of our research and drugs dealing with Alzheimer’s is completely wrong.
Those tau proteins that are associated with Alzheimer’s? It turns out they are critical for microtubules, which need to remain dynamic, always changing. Individual microtubules are comprised of stable and labile portions. And, there is more tau protein on the labile portion- so our hypothesis that tau is a microtubule stabilizer is simply wrong.
The theory before this research development was the folks with degenerative brain diseases lose microtubules, that these structures are less stable because of the disease. But, it turns out that when the tau proteins get depleted, patients are losing the dynamic regions of the microtubule. So, when we stabilize the microtubules, when we don’t let them change conditions, we are actually exacerbating their brain’s afflictions. (That’s probably why so many of the Alzheimer’s drug protocols have been failing- because they’ve been aimed at lowering tau levels- probably below that necessary to let the microtubules grow and change.)
We knew that in the affected brains, tau breaks away from the microtubules, forming what are called neurofibrillary tangles. Those tangles attenuate nutrient transport, so the neurons die a slow death. Which is why we thought we needed to keep the tau locked up, keeping the microtubules stable (where they work in axons, the ‘tentacles” of neurons), so they wouldn’t form the tau tangles.
The new research, summarized in “Tau Does Not Stabilize Axonal Microtubules but Rather Enables Them to Have Long Labile Domains”), was published in Current Biology. Drs. L. Qiang, X. Sun, T.O. Austin, H. Muralidharan, D.C. Jean, M. Liu, W. Yu, and P.W. Baas are the authors of this study and they hail from the Drexel University College of Medicine. (I remember when it was simply known as the Drexel Institute of Technology!)
Now, don’t get me wrong, we need both stable AND dynamic regions of the microtubules for cognitive functionality. And, that’s why our brains have accumulations of the tau protein.
But, this research involved depleting tau from rat neurons and examining microtubule levels in the axon after four days. Lo and behold, the volume of microtubules were reduced within the axon- but not because they were destabilized, but instead due to tau protein loss in the dynamic regions of the microtubules. The stable microtubule mass increased, but its labile portion is virtually depleted. The MAP6 (stable tubule-only polypeptide) becomes enriched on the stable portion- but also routinely spreads across the labile portion, where it normally is less present.
Yes, that means MAP6 is the stabilizer of the microtubules in the axons of the neuron- and it spreads across the microtubule as tau becomes depleted. And, tau, which is enriched in the labile domain, is critical to ensure the dynamic ranges change and prevent its stabilization, allowing nutrient transport to function well.
Just the opposite of what was considered to be true.
Interesting blog even though much of the language was beyond my comprehension…I’m a writer, not a scientist. So, are we any closer to discovering the cause of Alzheimer’ s and its cure? Personal interest here as I’ve lost father and sister to the disease and presently caring for brother in early-stage.
Well, Gay, it seems that we had the wrong hypothesis as to the genesis of Alzheimer’s. So, all the treatments we were developing were not directed at the true caus-e just what we thought was a symptom. Given this refinement, we can now aim at the more appropriate target- and hopefully be dead on.
Hopefully, with this new discovery and direction, a cure will be found!
From your mouth to God’s ears, Jyll!
thanks for sharing the knowledge. I recently read an article too on an early diagnostic test which would predict the possibility of Alzheimer’s. it’s good that our medical science is evolving. great post
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There is a great push to find an early diagnostic tool, Dr. M. But, in my mind, why would I want to know sooner that I have a disease for which there is no treatment or cure- yet?
I didn’t understand a word of this… really, but having lost my mum to Alzheimer’s I’d love to find out one day what the real cause is… and it wouldn’t surprise me if our food patterns are a major contributor.
So sorry I failed to explain the science more clearly, Saskia.
I don’t think our food patterns will have a major contribution, though, Saskia, since there is not a tremendous variation in incidence around the world.
How many times have we heard, “oops” from the medical community when they discover they were wrong or on the wrong track with what they thought? It makes me feel like we are all lab rats being tested on til they get it right.
I do understand that they have good intentions and that we can’t know if something is right or not until the results are in or something new is learned, and that makes it hard to trust that what we are being told is right.
All learning involves making mistakes. It is exactly how we learn to walk and talk. So. mistakes are critical to our learning and progression. The trick is to not hold on to the mistaken methods or thoughts too long, Julia.
Responding to your comment to Gay – my mother in law has early Alzheimers, and her doctor said “no, don’t put her on any of those drugs, they really don’t work”. And now I know he was right So sad, seeing a once vital woman go down a path none of us would ever have wanted us to go down.
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Yes, Alana. We need to know the how and the why before we can truly develop a cure or treatment.
That would be great if now they can find a cure! Alzheimer’s is so painful for the those watching their loved ones deteriorate, like my mom who I lost in 2000 from the dreaded disease.
Spot on, Martha! It is critical to know the cause so we can develop the treatment or cure!
A lot of it went over my head as any scientific knowledge that I seem to posses applies to plants, rather than humans. Nevertheless, I hope that scientists can figure out this mystery. It is very sad to watch my mom go through this nightmare.
It’s sad that anyone has to be subjected to the syndrome, Alice. Hopefully, this will help us get a solution.
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Thanks for the visit and the comment!