By Roberta B. Ness
About 18 months ago, my father died from complications of Alzheimer's disease. At age 12 he fled the Nazis with not a nickel in his pocket; at age 55, he was second in command at the Internal Revenue Service. By the end, his life had narrowed to a day-long plea to brush his teeth and go to bed.
Just months after his death, still grief-stricken, I gave a TED talk in Palm Springs about barriers to American innovation. "I kept thinking," I said, "I am a physician and scientist and I failed him. I cannot - we should not - accept science's impotence to solve [the cause of] Alzheimer's disease."
Now a radically new possible explanation for the cause of Alzheimer's disease has emerged - but I'll bet you'll find it less than reassuring.
What if Alzheimer's is caused by an infectious agent? What if that agent could be transmitted to your brain from another person through brain surgery or perhaps could even be transmitted to your brain by eating tainted meat. Could such nightmare scenarios be possible?
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To explain, let's turn back the clock to 1982. Stanley Prusiner, now at the University of California, San Francisco, proposed a radical explanation for the cause of a family of strange neurologic disorders that could be transmitted to mice or monkeys via injection of diseased brain tissue. Despite an exhaustive search, scientists had been unable to find in the diseased brains any foreign DNA or RNA representing an infection. Prusiner proposed a crazy idea (at least it seemed so at the time): "prions."
Prions are a class of proteins that exist in a normal cellular form but also can become misfolded. The misfolded form has only to touch the normal protein and it too misfolds, creating a cascade that turns brain cells into a spongy mess.
Creutzfeldt–Jakob disease (CJD) is a prion disease that affected an unfortunate group of children who, years ago got a contaminated batch ofhuman growth hormone. Mad cow disease - the technical term is bovine spongiform encephalopathy - is another prion disease that may sound more familiar. It has sickened and killed over 200 people who ate infected cattle in the early 1990s. Fortunately, new infections have been eliminated in the U.S. - as far as public health agencies know - by banning the feeding of meat and bone meal to cattle, import controls and the discarding by U.S. slaughterhouses of neurologic tissue from cattle.
Alzheimer's disease also has recently been recognized as a prion-associated disease. The hallmark pathology seen in the brains of people with Alzheimer's, amyloid-β and tau, turn out to also be misfolded proteins. But data showing that amyloid and tau might be contagious have been absent - until now.
What has been known for almost a decade is that injection of amyloid-β into mice seeds an abnormal build-up of amyloid in mice brains. Amyloid spreads from cell to cell within the brain. Mice, of course, are not human and so although this research has been accepted with interest, it has not raised any alarms.
Then last year, British researchers reported that the brains of patients who died from CJD (as a result of injections from the tainted growth hormone) contained an abnormally large number of amyloid deposits. The worrying conclusion from these observations: that the hormone injections might have transmitted prions causing CJD but also causing the build-up of amyloid and thus Alzheimer's. Amyloid build-up is known to proceed the symptoms of Alzheimer's by several decades, so the fateful growth hormone injections, which occurred in the 1960s-'80s might be showing up only recently.
You can just imagine how controversial all of this is, so don't take any of this as gospel. But if it is true, what makes it scary is that prions are terribly hardy. The normal procedures historically used to sterilize instruments used in brain surgery do not always destroy them. Equipment from brain surgery conducted on a patient with CJD or with Alzheimer's might at least hypothetically cause a subsequent patient to develop Alzheimer's 30 or 40 years down the road. Eating meat from cows with undetected mad cow disease, too, might hypothetically cause later Alzheimer's disease. No one knows if any of these speculative scenarios could occur.
The good news is that mad cow seems to have been eliminated from U.S.-supplied beef. Moreover, now that the possibility of contagion by brain surgery has arisen, scientists are scrambling to find out if there is any such risk and, if so, how to eliminate it. No one wants to consider the specter of having been accidentally infected decades ago - and thus being at risk for developing Alzheimer's disease in the future. But if such things happened in the past, at least that knowledge will allow us to find ways to prevent such a cause for Alzheimer's in our children.
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