Reducing Amyloid Plaque Burden via Ex Vivo Gene Delivery of an Aβ-Degrading Protease: A Novel Therapeutic Approach to Alzheimer Disease (original) (raw)
Figure 5
Reduction in Hippocampal Plaque Burden following sNEP Cell Engraftment
Aged J20 APP transgenic mice were implanted with fibroblasts expressing either sNEP (n = 5) (A, C, E, and G) or GFP (n = 3) (B, D, F, and H). Cells were stereotaxically placed into the right (ipsilateral, right) hippocampus, with the uninjected left (contralateral, left) hippocampus serving as control. Brains were harvested for analysis 28 d after surgery. Grafted cells were immunoreactive for either NEP (A) or GFP (B), with superior and inferior aspects of the graft, respectively, indicated by arrows. Images (C–H) show staining for plaque burden at sites medial to the graft (C and D), at the site of the graft (E and F), and at sites lateral to the graft (G and H). These fields were quantified by calculating the ratio of the area covered by plaques on the ipsilateral versus the contralateral side; quantification was done in a blinded fashion. This ratio was determined separately for the sNEP and GFP groups and compared at the hippocampus medial to the graft (I), the graft site (J), and the hippocampus lateral to the graft (K). Data represent the ratio's mean ± SEM, compared to GFP control: ** p = 0.0020 for the medial hippocampus (I); * p = 0.0269 for the graft site (J); and ** p = 0.0081 for the lateral hippocampus (K).