The presence of β-amyloid plaques has long been associated with Alzheimer’s disease, but the question, “Do these plaques cause the disease or just correlate with it?” has not been answered. This paper shows that a form of the β-amyloid protein other than that found in the plaques causes initial memory loss.

  Does it describe a new discovery, methodology, or synthesis of knowledge?

“Today 4.5 million Americans suffer from Alzheimer's disease, and many more are affected by it when you consider the toll it takes on family caregivers, social agencies and medical service providers.”

Yes, it does all three. First, it describes Aβ*56, the first Aβ species isolated from brain tissue shown to impair memory. Second, it describes new methodology for isolating Aβ species from source material, and for assaying its effects on brain function. Third, it describes a hypothesis—that Aβ*56 initiates Alzheimer’s disease—which may help us better understand the boundary between age-associated memory impairment and the onset of Alzheimer’s disease.

Beta-Amyloid protein (Aβ) is a naturally occurring substance in the brain. In Alzheimer’s disease, something causes this protein to clump together and form sticky plaques. Why the plaques form and what role they play in memory loss is not known.

We discovered Aβ*56, a particular form of the Aβ protein. It is present in the brains of laboratory animals genetically modified to develop aspects of very early Alzheimer’s disease.

Aβ*56 appears in the brain at the very same time that memory loss begins and yet before the plaques develop. We were able to identify Aβ*56, purify it, and apply it to healthy laboratory animals, which then developed memory loss.

This is the first time that a substance was identified and proven to cause memory loss in a laboratory model of Alzheimer’s disease.

Fifteen years ago, I started researching Alzheimer’s disease, because the loss of memory and cognitive function really does seem to steal a person's identity. I chose to study not only the structural effects of the disease in the brain, but also the functional effects of the disease.

At the time, there were no transgenic models of Alzheimer’s and so we had to create one in order to study the effects of the disease on brain function. Since then, we have slowly gained understanding of what happens biochemically and pathologically inside the brain and how they impact cognitive function.

We still have a long way to go to really understand the mechanisms causing Alzheimer’s disease, but I am pleased to have chosen the task of identifying the molecular basis of memory loss when not many other laboratories were doing this.

  Are there any social or political implications for your research?

Today, 4.5 million Americans suffer from Alzheimer's disease, and many more are affected by it when you consider the toll it takes on family caregivers, social agencies, and medical service providers. It is the third most expensive disease to treat in America.

By 2050, the number of people with the disease will increase fourfold unless we can prevent or cure it. If we can design a drug or vaccine to block Alzheimer’s disease before it develops, millions of people will be able to live the last years of their lives with their memories and cognitive functions intact.