Imaging technique could help to resolve questions about brain plaques associated with the condition.
An imaging agent that reveals a signature of Alzheimer’s disease in the brain — given conditional support last week by advisers to the US Food and Drug Administration (FDA) — is likely to be more valuable to scientists than to patients.
The agent, called florbetapir (Amyvid), enables physicians to determine whether Alzheimer’s disease is the cause of a patient’s dementia. In the future, it may also help them to catch the disease before obvious symptoms appear, a hope that has sparked fresh debate about the value of early diagnosis for a devastating, untreatable disease. The panel of advisers — whose guidance is usually, but not always, followed by the FDA — also stated that the test should not be given final approval until its developers demonstrate that clinicians can uniformly interpret its results.
“The importance of the decision is probably bigger for research in the near future than it is for clinical practice,” says William Thies, the chief medical and scientific officer of the Alzheimer’s Association based in Chicago, Illinois, a nonprofit organization that funds research on Alzheimer’s disease.
Physicians diagnose Alzheimer’s disease only after memory loss interferes with daily activities. By then, “there’s so much irreversible damage that it might be too late to hope for an effective treatment”, says Gil Rabinovici, a neurologist at the University of California, San Francisco. Definitive confirmation comes from autopsy, with the presence of characteristic lesions in the brain caused by clumps of the peptide amyloid-β. These amyloid plaques are hypothesized to be the cause of the memory loss.
Some researchers already use a reagent called Pittsburgh Compound B to image amyloid plaques in people suspected to have Alzheimer’s disease. The compound binds to the plaques, and its radioactivity can be detected using positron emission tomography. But the reagent is labelled with carbon-11: with a half-life of just 20 minutes, its use is limited to the handful of facilities that have an on-site cyclotron to prepare it.
In contrast, florbetapir is labelled with fluorine-18, which has a half-life of nearly two hours. That would be long enough to allow the compound’s manufacturer, Eli Lilly, based in Indianapolis, Indiana, to send labelled florbetapir directly to users without losing too much of the reagent to radioactive decay. The likely result: more and bigger studies of the relationship between amyloid and disease, says Thies.
A study published last week was crucial to the advisory panel’s decision. It confirmed that brain scans of living patients given florbetapir correlate with amyloid plaques found at autopsy after they died (C. M. Clark et al. J. Am. Med. Assoc. 305, 275–283; 2011 ). The Alzheimer’s Disease Neuroimaging Initiative, a project to improve clinical trials of candidate therapies for Alzheimer’s disease, has already incorporated florbetapir in its studies of hundreds of people suspected to have the condition. And Rabinovici hopes to test whether the reagent can distinguish between Alzheimer’s disease and frontotemporal dementia, which causes many of the same symptoms and is often misdiagnosed.
Florbetapir could help to resolve one of the fundamental disputes about Alzheimer’s disease: whether amyloid plaques kill brain tissue or are a side effect of the disease process. “Critics always tell me ‘well we don’t know yet if the amyloid hypothesis is true’,” says William Jagust, a neuroscientist at the University of California, Berkeley. “But this compound will finally allow us to examine just how important amyloid is.”
source: nature medicine