Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes

Doubly transgenic mice (PSAPP) overexpressing mutant APP and PS1 transgenes were examined using antibodies to A beta subtypes and glial fibrillary aci dic protein (GFAP). Visible A beta deposition began primarily in the cingul ate cortex of PSAPP mice at approximately 10 weeks of age. By 6 months, the mice had extensive amyloid deposition throughout the hippocampus and corte x as well as other regions of the brain. Highly congophilic deposits consis ting of N-terminal normal and modified forms of A beta were identified, rem iniscent of those found in human AD brain. Both immunohistochemistry and ma ss spectrometry showed that A beta 42 forms were underrepresented relative to A beta 40, and A beta 43 was undetectable. Deposits were associated with prominent gliosis which increased with age, but in 14-month-old PSAPP mice , GFAP immunoreactivity in the vicinity of amyloid deposits was substantial ly reduced compared to APP littermates. These mice have considerable utilit y in the study of the amyloid phenotype of AD. (C) 1999 Academic Press.