BIOCHEMICAL AND COGNITIVE STUDIES OF APOLIPOPROTEIN-E-DEFICIENT MICE

Apolipoprotein-E-deficient mice provide a useful model system for stud ying the role of apolipoprotein E (apoE) in brain function. In the pre sent study, we characterized the cholinergic function of these mice an d the extent of phosphorylation of their cytoskeletal protein tau. Mor ris water maze tasks revealed deficits in working memory that were acc ompanied by a specific decrease in hippocampal and cortical choline ac etyltransferase activities. Immunoblot experiments utilizing native an d dephosphorylated tau and antibodies directed against specific phosph orylated and unphosphorylated tau epitopes revealed that tau of the ap oE-deficient mice is hyperphosphorylated. These results show that apoE -deficient mice have cognitive cholinergic and cytoskeletal derangemen ts and point out the importance of this model for studying the role of apoE in neuronal function.