Figure 7.
Enhanced BACE1 retrograde transport reduces synaptic Aβ levels in mutant hAPP Tg mouse brains. A, Greater enrichment of Aβ40 in the synapses of hAPP mouse brains. Human Aβ40 levels were measured in the synapse-enriched synaptosomal preparations and postnuclear supernatants from hAPP mouse brains by ELISA assay (n = 6). The concentration of synaptic Aβ40 in the hippocampus was compared with and normalized to that in PNS from the same hAPP mice. B, Reduction of human Aβ40 levels at synaptic terminals in the hippocampus of mutant hAPP mice transduced with AAV-Snapin (n = 6 for each genotype). C, D, Quantitative analysis (C) and representative images (D) of intracellular Aβ in hAPP mice injected with AAV and AAV-Snapin. Note that elevated Snapin expression reduced aberrant accumulation of intracellular Aβ in the hippocampal regions of AD mice. White arrows marked soluble Aβ clusters in the hippocampal mossy fibers of hAPP mice. The mean intensity of anti-A11-stained intracellular Aβ oligomers was quantified and compared to that of controls from a total number of 56–57 imaging slice sections per genotype. s.p., Stratum pyramidale; mf, mossy fiber. E, F, Representative images (E) and quantitative analysis (F) showing reduced amyloid deposition in the hippocampal regions of hAPP mice expressing AAV-Snapin by immunostaining using anti-6E10 antibody. The percentage of plaque coverage area was quantified from a total number of 43–47 imaging slice sections per genotype, and the results are expressed as the percent difference from hAPP mice injected with AAV control. Scale bars: 25 μm. Error bars represent SEM. *p < 0.05; **p < 0.01; ***p < 0.001 (Student's t test).