Imaging of Aβ plaques in the brain of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease of the brain with symptoms including dementia, cognitive impairment and memory loss. Formation and accumulation of aggregates of beta-amyloid (Abeta) peptides in the brain are critical factors contributing to the development and progression of AD. Cognitive decline and behavioral changes related to old age and AD are often very difficult to differentiate. Currently, there is no simple and definitive imaging tool available to assist the diagnosis. Recent reports suggest that accelerated accumulation of Abeta plaques in the brain may be a key risk factor associated with AD. Therefore, there is an urgent need for in vivo imaging agents, which are valuable as specific biomarkers to demonstrate the location and density of amyloid plaques in the living human brain. Recent advances in developing tracers for binding Abeta plaques suggest that there are specific and saturable binding sites on the aggregates of Abeta peptides that can be selectively labeled and imaged in vivo. Several Abeta-specific binding agents, which are derivatives, including naphthalene, benzothiazole, stilbene or other related heterocyclic derivatives containing an electron-donating group on one of the aromatic rings, are useful candidates. A novel series of stilbenes, which are simple, relatively small, neutral and lipophilic molecules, are reported. Oil the basis of their exquisitely high binding affinity to Abeta(1-40) aggregates (K-i at the range of 0.1-20 nM), they are suitable candidates as Abeta plaque-selective imaging agents. More importantly, they also showed an ability to penetrate the intact blood-brain barrier, an essential prerequisite for a useful plaque-imaging agent. The Abeta plaque-specific imaging agents will be useful for early detection or monitoring the progression and effectiveness of treatment of AD. (C) 2004 Elsevier B.V. All rights reserved.