FIGURE 1.

Common cellular changes detected in the central nervous system of Down syndrome (DS)/Alzheimer disease (AD) subjects compared to controls. (A) 1. Endosomal body/multivesicular body (MVB) processing in normal individuals. 2. Uncorrupted lysosome (LYS)‐mediated degradative system. (B) 1. Altered endosome pathway. Individuals with DS/AD manifest changes and impairments in cargo sorting and metabolism from early endosomes (EEs) or late endosome (LEs) to MVBs toward the degradation pathway, resulting in increased number and enlargement of EEs, LEs, and MVB, and increased exosome production and release. 2. Degradative pathway defects. Proteolysis and recycling deficit in DS/AD result from selectively impaired lysosomal degradation of cellular material. APP = amyloid‐β precursor protein. [Color figure can be viewed at www.annalsofneurology.org]