In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease

Strategies for treating Alzheimer's disease (AD) include therapies designed to decrease senile plaque (SP) formation and/or promote clearance of SPs. but clinical trials of these treatments are limited by the lack of effectiv e methods to monitor changes in plaque burden in the brains of living AD pa tients. However. because SPs are extracellular deposits of amyloid-beta pep tides (A beta), it may be possible to eventually develop radioligands that cross the blood-brain barrier (BBB) and label SPs so they can be visualized by current imaging methods. As a first step toward the generation of such a radioligand, we developed a probe, [(trans,trans)-1-bromo-2,5-bis-(3-hydr oxycarbonyl-4-hydroxy)styrylbenzene(BSB)], and we report here that BSB has the following properties essential for a probe that can detect SPs in vivo, First, BSB sensitively labels SPs in AD brain sections. Second. BSB permea tes living cells in culture and binds specifically to intracellular A beta aggregates. Third, after intracerebral injection in living transgenic mouse models of AD amyloidosis. BSB labels SPs composed of human A beta with hig h sensitivity and specificity. fourth, BSB crosses the BBB and labels numer ous AD-like SPs throughout the brain of the transgenic mice after i.v. inje ction. Thus, we conclude that BSB is an appropriate starting point for futu re efforts to generate an antemortem diagnostic for AD.