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The red pill of Alzheimer's: Would you take it?

An international team of experts on Alzheimer's disease uncovers a gene variation that reveals the rate at which the disease will progress.

Elizabeth Armstrong Moore
Elizabeth Armstrong Moore is based in Portland, Oregon, and has written for Wired, The Christian Science Monitor, and public radio. Her semi-obscure hobbies include climbing, billiards, board games that take up a lot of space, and piano.
Elizabeth Armstrong Moore
3 min read
Michael Carian documents the progression of his grandfather Fred Carian's Alzheimer's disease. carianoff/Flickr

It appears that a single gene variation provides clues as to how rapidly Alzheimer's disease will progress, according to an international investigation of tau proteins in cerebrospinal fluid (CSF), which was led by Washington University School of Medicine in St. Louis. The findings were reported online yesterday in the journal Public Library of Science Genetics.

It has recently been established in multiple studies that elevated levels of this protein in cerebrospinal fluid indicate Alzheimer's, and that because symptoms can reveal themselves slowly, testing levels of tau would offer a glimpse into the future--a red pill, if you will, on the nature of our own cognition as we age.

But the red pill has grown more sophisticated. It seems we can now tell not only whether we carry some dormant beginnings of Alzheimer's within, but also whether it will progress slowly or more like wildfire.

"Until now, most studies of genetic risks associated with Alzheimer's disease have looked at the risk of developing the disease, not the speed at which you will progress once you have it," says senior investigator Alison Goate. "The genetic marker we've identified deals with progression."

When neurofibrillary tangles form, brain cells die and release the protein tau, elevated levels of which indicate neurological diseases such as Alzheimer's. National Institute on Aging

The team of experts analyzed 846 patients with elevated levels of tau, looking specifically at single DNA variations. What they discovered was that a genetic marker--a phosphorylated form of the protein (ptau)--is associated with rapid progression of the disease, and those who carry this marker have higher tau levels at all stages of the disease than those who do not.

"We have looked at data from three separate, international studies, and in all three, we found the same association," says first author Carlos Cruchaga, an assistant professor of psychiatry at Washington University. "So we are confident that it is real and that this gene variant is associated with progression in Alzheimer's disease. Other neurodegenerative conditions, like Parkinson's disease, don't produce elevated ptau in the CSF. It's only found in Alzheimer's disease."

In their news release, the authors suggest that knowing the rate of progression may actually be more useful than knowing whether the disease is present, because dealing with mild impairment is entirely different (for the afflicted as well as the caregivers) than dealing with severe dementia.

For those who prescribe to the blue pill approach when it comes to aging and death, there may be some comfort in knowing that in our lifetime we may be able to decrease or manipulate ptau in such a way as to at least slow the progression of Alzheimer's, the researchers say.

And as with so many diseases, the earlier the diagnosis, the greater the chance of survival--or, to be more accurate, postponement.

I am reminded of the September 10, 2001 New Yorker essay, My Father's Brain, by Jonathan Franzen, who belongs to that rare breed of authors who make the cover of Time and inspire all sorts of intellectual crushes (OK, mine), and who happens to hail from St. Louis, where this research was conducted.

In the essay, which happened to be published the day I turned 22, which was the day before the towers fell and the country began to undergo its own experiment in the collective memory of tragedy, Franzen describes dealing with a parent afflicted by Alzheimer's more elegantly than anything I've yet read on the subject:

After we'd kissed him goodbye and signed the forms that authorized the brain autopsy, after we'd driven through flooding streets, my mother sat down in our kitchen and uncharacteristically accepted my offer of undiluted Jack Daniel's. "I see now," she said, "that when you're dead you're really dead." This was true enough. But in the slow-motion way of Alzheimer's, my father wasn't much deader now than he'd been two hours or two weeks or two months ago. We'd simply lost the last of the parts out of which we could fashion a living whole. There would be no new memories of him. The only stories we could tell now were the ones we already had.

If you had the chance, would you take the red pill? Save your loved ones the pain of guessing? The legions of people who suffer through colonoscopies and mammograms and biopsies suggest that many of us would. It's the yearning to know so that we might better manipulate the outcome.

So the question then becomes, what do we do if we carry the marker that points to rapid decline? It is the ultimate irony--not wanting to lose self-awareness, yet suffering because of it.