Expression of transgenic APP mRNA is the key determinant for beta-amyloid deposition in PS2APP transgenic mice.

Alzheimer's disease is the most common cause of dementia occurring in the elderly. The identification of the genetic factors in the familial forms of the disease enabled the generation of transgenic animals which reproduce an essential part of its pathology. Various lines of transgenic mice expressing human wild-type or mutated APP have been reported. The phenotype expressed in these mice varies according to the transgene itself, the promoter used for its expression, and the level of expression achieved in the brain, but is also determined by the genetic background of the mice. We analyzed the variability in the amyloid load by ELISA and the levels of huAPP transcripts by quantitative PCR in our PS2APP double-transgenic mice when expressed in a mixed C57Bl/6, DBA/2 background. In 12-month-old PS2APP double-transgenic mice, the amount of cerebral amyloid deposits is directly correlated with the levels of the huAPP transgenic transcript. Furthermore, a reduction in human APP transcripts by 50% leads to a complete absence of cerebral deposits at the age of 12 months. Our results demonstrate that a 2-fold reduction in APP expression can result in a profound decrease in brain pathology.