The Plaque is the Culprit

There has been much excitement in the nuclear medicine community over the new PET imaging agents that are designed to attach to the amyloid plaque in Alzheimer's disease. Both FDDNP and the Pittsburgh compound B have shown that nuclear medicine can be used for early detection of plaque burden and possibly as a way of monitoring disease progression or efficacy of potential plaque dissolving agents.

The "fly in the ointment" is that there is still some controversy over whether these plaques are the cause of Alzheimer's or simply a side effect of the disease. So it was with interest that I read a press release from researchers as MassGeneral Institute for Neurodegenerative Disease (MGH-MIND). Working with colleagues from Washington University School of Medicine, the researchers showed that Alzheimer's-associated neuronal changes appear soon after the development of plaques.

In their research, which appeared in the Feb. 7 issue of Nature, the researchers used a novel technique for microscopically imaging the brains of living animals. Using several strains of transgenic mice destined to develop amyloid plaques, they imaged initially plaque-free areas of the brain on a regular basis --first weekly and, in subsequent experiments, daily. Although plaques formed rarely, they could appear as little as 24 hours after a previous plaque-free image was taken.

The new plaques were similar in appearance to those seen in the brains of Alzheimer's patients and in the mouse models, and subsequent imaging showed little change in the size of plaques once they had formed. Examining neurons adjacent to plaques showed that the kind of changes associated with Alzheimer's--distortions in the projections through which neuronal signals pass--appear rapidly and approach maximum effect within five days.

"These results confirm the suspicion we've had that plaques are a primary event in the glial and neuronal changes that underlie Alzheimer's dementia," said Bradley Hyman, MD. PHD, director of the Alzheimer's unit at MGH-MIND. "We hope that what we've learned about the time frame and sequence of events will help us find ways to keep plaques from forming."

Go to http://www.massgeneral.org/news/releases/020608hyman.html for more on this study.

Meanwhile, now that the nature of the plaques has been visualized, it should help in the research and eventual regulatory review of these new plaque imaging agents. Or at least that is what I hope. What do you think?