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Figure 5


Fig. 5. Macroautophagy is impaired in the PS1-APP mouse model of AD. (A, arrows) Immature AVs accumulate during the early evolution of pathology in a dendrite. (B) Punctate structures exhibiting strong LC3 immunofluorescence can be seen in neurites of PS1-APP mice (arrows) and especially in the swollen dystrophic dendrites of cortical pyramidal neurons. (C) Development of neuritic dystrophy in AD brain. Endocytic trafficking and autophagy are both normally active in neuronal processes. Nascent AVs mature to autophagolysosomes during their retrograde transport, fusing with anterogradely transported lysosomes. Pathological AV accumulation is associated with inhibited retrograde AV transport and impaired autophagosome-lysosome fusion. Fusion of some accumulated AV compartments with the plasma membrane may contribute to local membrane expansion. Bars, 500 nm (A); 10 µm (B). Panels A and B reprinted with permission (Yu et al., 2006).





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