CLUSTERIN (APE-J) PROTECTS AGAINST IN-VITRO AMYLOID-BETA(1-40) NEUROTOXICITY

Clusterin is a secreted glycoprotein that is markedly induced in many disease states and after tissue injury. In the CNS, clusterin expressi on is elevated in neuropathological conditions such as Alzheimer's dis ease (AD), where it is found associated with amyloid-beta (A beta) pla ques. Clusterin also coprecipitates with A beta from CSF, suggesting a physiological interaction with A beta. Given this interaction with A beta, the goal of this study was to determine whether clusterin could modulate A beta neurotoxicity. A mammalian recombinant source of human clusterin was obtained by stable transfection of hamster kidney fibro blasts with pADHC-9, a full-length human cDNA clone for clusterin. Rec ombinant clusterin obtained from this cell line, as well as a commerci al source of native clusterin purified from serum, afforded dose-depen dent neuroprotection against A beta(1-40) when tested in primary rat m ixed hipppocampal cultures. Clusterin afforded substoichiometric neuro protection against several lots of A beta(1-40) but not against H2O2 o r kainic acid excitotoxicity. These results suggest that the elevated expression of clusterin found in AD brain may have effects on subseque nt amyloid-beta plaque pathology.