ARTIFACTUAL STRAIN-SPECIFIC SIGNS OF INCIPIENT BRAIN AMYLOIDOSIS IN APP TRANSGENIC MICE

In an attempt to generate transgenic mice modeling Alzheimer-type amyl oidogenesis, the COOH-terminal 103 residue human AFP segment was expre ssed in brain regions known to be vulnerable in AD. Transfected cells overexpressing this transgene were previously shown to develop intracy toplasmic inclusions that were immunoreactive with antibodies to the A FF COOH-terminus. Transgenic C57B6/SJL mice produced transgene-coded m RNA in their brains at levels up to sixfold above endogenous APP, most abundantly within cortical and hippocampal pyramidal neurons. Immunoc ytochemistry with anti-A beta antibodies revealed occasional structure s that resembled diffuse amyloid, but which could not be detected on s erial sections. Immunolabeling with antibodies to AFP regions NH2-term inal to the transgene-coded domain revealed elevated immunoreactivity within perikarya and neurites in regions expressing the highest transg ene and endogenous APP mRNA levels, similar to observations previously reported within vulnerable neurons in AD brain. However, subsequent b reeding revealed that this phenotype segregated with the B6/SJL backgr ound rather than the transgene, thus emphasizing the importance of gen etic background to observations of putative AD-type pathology in trans genic animals.