Clusterin (Apo 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 expression is elevated in neuropathological conditions such as Alzheimer's disease (AD), where it is found associated with amyloid-beta (A beta) plaques. 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 fibroblasts with pADHC-9, a full-length human cDNA clone for clusterin. Recombinant clusterin obtained from this cell line, as well as a commercial source of native clusterin purified from serum, afforded dose-dependent neuroprotection against A beta (1-40) when tested in primary rat mixed hippocampal cultures. Clusterin afforded substoichiometric neuroprotection against several lots of A beta (1-40) but not against H2O2 or kainic acid excitotoxicity. These results suggest that the elevated expression of clusterin found in AD brain may have effects on subsequent amyloid-beta plaque pathology.
Boggs
L N
LN
Lilly Research Laboratories, CNS Research Division, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Fuson
K S
KS
Baez
M
M
Churgay
L
L
McClure
D
D
Becker
G
G
May
P C
PC
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002460:Cell Line / Q000502:physiology; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000494:pharmacology / Q000502:physiology*; D006224:Cricetinae; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D014162:Transfection
D016229:Amyloid beta-Peptides; C495242:CLU protein, human; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins