Figure 1

The McGill-R-Thy1-APP transgenic rat phenotype. (A) The McGill-R-Thy1-APP transgenic rat expresses the human APP751, bearing the Swedish and Indiana mutations under the control of the murine Thy1.2 promoter. Its phenotype is fairly similar to the human pathology reported in AD and MCI. (B) We observe intraneuronal Aβ accumulation starting at 1 week post-natal, as determined with our murine monoclonal antibody (McSA1) against the N-terminus of the Aβ peptide. The development of plaques follows the same anatomical sequence as in humans. Mature amyloid plaques are Thioflavin S-positive (C) and are surrounded by activated microglia as observed with MHCII- (brown) and Aβ-specific antibodies (McSA1-blue) and also with Iba-1(blue) and McSA1(blue) (D). Plaques are also accompanied by dystrophic neurites (E) and astrogliosis (GFAP-blue, McSA1-green) (F). (G) These rats already show learning deficits in the Morris water maze task at the pre-plaque stage (3 months old) and these deficits progress with amyloid accumulation. Images adapted from [81] with the publisher’s permission and from [83].