I was intrigued, and a bit alarmed, by a study in this month’s Archives of Neurology. The study used an imaging agent called Pittsburgh Compound B (so-named because it was discovered at the University of Pittsburgh; it detects brain deposits that the conventional medical wisdom claims is the cause of Alzheimer’s disease) to examine the brains of 43 people, age 65 to 88, who had neither Alzheimer’s disease nor mild cognitive impairment. Of the 43, 9 showed evidence of these brain deposits, called amyloid plaques, in at least one brain area.
Uh oh, you might think. But think again. Here is what caught my attention in the paper describing the study: “Neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. . . . [A]myloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal.”
So here’s the reason for my alarm: since Pittsburgh Compound B has, since its discovery, been treated like the Second Coming, do we really want to screen people with this technique, telling them omigod you have amyloid plaques—when the cause-and-effect link between the plaques and Alzheimer’s is, shall we say, on shaky ground? Or as the scientists, led by Howard Jay Aizenstein and William E. Klunk of the University of Pittsburgh School of Medicine, write, we’ll need more research to figure out whether “amyloid deposition is not sufficient to cause Alzheimer disease.”
The amyloid hypothesis of Alzheimer’s disease has had the field in a stranglehold for decades, as I’ve written about before. In 2006, for instance, Zaven Khachaturian, who oversaw Alzheimer’s funding at the National Institute on Aging from 1977 to 1995, told me that the theory that amyloid plaques cause AD has become a pernicious “orthodoxy,” and that “having one view prevail is harmful; it becomes a belief system, not science.” And Robert Mahley, president of the J. David Gladstone Institutes, San Francisco, told me that “where the field made its mistake was in trying to make everything fit one common [amyloid] pathway. We’ve got to realize there are multiple ways you can wind up with [Alzheimer’s].”
They, and others, are most upset about what the amyloid orthodoxy has meant for basic research--namely, that scientists with other ideas struggled to get funded. As a result, alternatives have hardly been pursued, and we are no closer to treating, let alone preventing or curing, AD than we were 25 years ago. That’s a tragedy, and perhaps a crime.
But what will the amyloid orthodoxy mean for patients? If it is moved into the clinic with the use of Pittsburgh Compound B, and healthy adults are screened for amyloid plaques with this technique, we'll face a problem just as serious as focusing on a single theory of AD. Doctors will identify these brain deposits in millions of people, and scare them out of their wits by telling them that they have what looks like the cause of a terrifying disease—when the whole idea that the plaques cause AD may be wrong?
Klunk put it this way: “The good news is it appears the brain can tolerate these plaques for years before the effects are apparent. The bad news is that by the time the symptoms emerge, the disease has had perhaps a 10-year head start. We suspect that people with amyloid deposits and normal brain functioning have a high risk of developing Alzheimer’s disease in the future, but we do not yet have proof of this.” No kidding.
