Scientists have been racing to develop simple, non-invasive, and accurate tools for the early diagnosis of Alzheimer's disease (AD). Recently, brain imaging has received a boost by the findings of Silverman et al, which showed that positron emission topography (PET) measurements of glucose metabolism could predict progression from cognitive impairment to dementia. Still lacking, however, is a selective molecular marker that would facilitate imaging of the amyloid plaques and neurofibrillary tangles (NFT) that are hallmarks of the disease (see related news item for a candidate). Now a new probe, FDDNP, developed by Jorge Barrio and colleagues at UCLA and the University of Ljubljana, Slovenia, promises to deliver such images.
In January's American Journal of Geriatric Psychiatry, Barrio et al. report, for the first time, the use of FDDNP to image plaques and NFTs in vivo. They show that the probe, which rapidly crosses the blood-brain barrier, was statistically slower in clearing the brain tissue of Alzheimer's patients than healthy controls. Moreover, PET scans that revealed regions of slower clearance and hence higher levels of plaques and NFTs, correlated well with regions that exhibited poorer glucose metabolism and hence lower neuronal activity. Postmortem analysis on one of the study's participants with AD allowed the researchers to directly correlate FDDNP binding with plaque and NFT lesions, though this data is still unpublished.
Eventual approval of FDDNP for routine diagnostic purposes will require full evaluation of its biochemical and toxicological properties, see commentary.—Tom Fagan
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- Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35. PubMed.