CHLOROQUINE ADMINISTRATION IN MICE INCREASES BETA-AMYLOID IMMUNOREACTIVITY AND ATTENUATES KAINATE-INDUCED BLOOD-BRAIN-BARRIER DYSFUNCTION

The anti-malarial drug chloroquine (CHL) has been reported to cause th e accumulation of beta-amyloid peptide containing fragments (fA beta) of the amyloid precursor protein within lysosomes in vitro. However, t he significance of this finding with regards to the development of Alz heimer's disease (AD) pathology in vivo is not known. Hence, we invest igated the effects of chronic CHL administration in the mouse. Systemi cally administered CHL caused an astrocytic response and an increase i n intracellular A beta immunoreactivity throughout the brain, but no p laque-like pathology. Pharmacological challenge with the excitotoxin k ainic acid (KA) revealed a mild proconvulsant effect of CHL pretreatme nt (P < 0.06). Interestingly, CHL protected the blood-brain barrier fr om characteristic KA-induced dysfunction. Given the hypothesized invol vement of both excitotoxic processes and the vascular system in AD, th e observed interactions may assist in elucidating the pathogenesis of AD. (C) 1997 Elsevier Science Ireland Ltd.