For Nerds Only -- Why does Alzheimer's disease advance more quickly in some than others?

I get different feedback on my blog content from different people.  Some are interested in the details I have about new research, but others are interested in my progress and in stories about living with dementia.  This post will be more interesting to the former ... the nerds.  But I'll be relatively brief.

A question is, why does Alzheimer's disease advance so much more quickly in some people than in others -- sometimes by a factor of 10?  One answer seems to be in the tau protein.

A little refresher.  Tau protein is essential to holding the "microtubules" together.  The microtubules act as a skeleton in the cell to give it shape, among other functions.  (We discuss this in Beating the Dementia Monster, complete with a little picture.)  If an abnormal form of tau protein is present and it fails, the microtubules collapse into the tangles that Alois Alzheimer saw in the brain autopsy of Auguste Deter in 1906.

You will also recall that Alzheimer's disease probably advances for 15 or more years before the first symptoms appear.  During that time, beta amyloid is leaving brain cells to eventually accumulate as plaques on brain cells.  Alzheimer saw these plaques as well.  But there is a tipping point in the advance of the disease that coincides with the first evidence of cognitive decline.

It is at this point that abnormal tau protein is expelled from cells to "seed" in other parts of the brain.  It's also a point in which the beta amyloid begins to agglomerate as plaques.  But it's this spread of tau protein in the brain that is under increasing scrutiny to explain how the disease advances.

There was an article in the June 22 issue of Nature Medicine that evaluates how different species of tau protein could be involved in more or less rapid propagation of tau in the brain -- and more or less rapid advance of dementia.  The article is not yet available on line, but it was reviewed in this week's ALZForum.  I won't try to go into detail about the research, but you can read all about it here.

The article points out one practical application of this knowledge in regard to trials of therapeutics.  In a trial, you want to know how rapidly the disease can be expected to advance so you can know if your therapeutic is a factor.  If the disease is advancing at a slow rate, is it because the study therapeutic is slowing it down, or was it going to advance slowly anyway?  There will be great variability among test subjects as to who will advance more quickly without the study therapeutic depending on which species of tau protein they possess.  Fortunately, a person's tau can be typed, and in so doing researchers will be able to tell what speed of advance to expect without the study therapeutic.