Alzheimer's abnormal brain proteins glow

HELEN R. PILCHER

Amyloid plaques often appear before clinical symptoms. © SPL

A new test takes a step towards diagnosing Alzheimer's disease in living patients. In mice it reveals amyloid plaques - a telltale sign of this type of dementia¹.

A test would help doctors to catch the disease early on, when therapies may be more effective. Currently, Alzheimer's can be confirmed only after death - doctors use cognitive tests and brain scans to assess memory-impaired patients, with about 85% accuracy.

Brain plaques appear before clinical symptoms, so something like the mouse screen could catch the disease before memory begins to falter. "We'll be able to design better drug trials," says test co-developer Brian Bacskai of Massachusetts General Hospital, Boston.

Bacskai injected a fluorescent molecule called Pittsburgh Compound B (PIB) into mice with a form of Alzheimer's disease. Their plaques lit up within minutes and could be seen by using a powerful microscope that peers through the skull.

Researchers from the same team are developing the test for human use. The microscope can only reveal half a millimetre into the brain, so clinical trials would use a positron-emission tomography (PET) scanner to probe more deeply. PET scans cannot detect florescence, so the molecule will be linked to a radioactive tracer, such as carbon-11.

"Early, failsafe diagnosis is necessary for drug development," says Susanne Sorensen, head of research at the Alzheimer's Society, a charity based in London. It would allow patients, at similar stages of the disease, to be selected for clinical trials.

A similar test for the second hallmark of Alzheimer's - tau protein tangles - is also needed, says Simon Lovestone, who studies ageing at Kings College London. Together, the markers could monitor disease progression, helping researchers to understand how changes occur in the demented brain.

You couldn't use the handful of UK PET scanners to test all the Alzheimer's sufferers Simon Lovestone Kings College London

Some 750,00 people in Britain suffer from Alzheimer's disease. "With the best will in the world, you couldn't use the handful of PET scanners in the UK to test them all," Lovestone says. A cheaper, easier approach will be needed.

Globally, Alzheimer's disease affects about 1 in 20 people over the age of 65, and nearly half of over-85s. Memory fails, followed by a decline in movement and reflexes. The disease is becoming a major health concern in rapidly ageing Western populations.

1. Bacskai, B.J.Four-dimensional imaging of brain entry, amyloid-binding and clearance of an amyloid-B ligand in transgenic mice by using multiphoton microscopy. Proceedings of the National Academy of Sciences, published online, doi:10.1073/pnas.2034101100 (2003). |Article|

© Nature News Service / Macmillan Magazines Ltd 2003