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During the first 100 years of Alzheimer's disease research, this devastating and intractable disorder has been characterized at the clinical, histological, and molecular levels. Nevertheless, many key mechanistic questions remain unanswered. Here we will emphasize the importance of the cell biology of Alzheimer's disease, reviewing the relevant literature that has expanded our mechanistic understanding, with a particular focus on pathways regulating protein sorting. Accumulated evidence indicates that sorting pathways may be uniquely vulnerable to disease pathogenesis, and recent studies have begun to reveal disease-related defects in the regulation of protein sorting.

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Petsko (TEDMED)Gregory Petsko knows why he came to TEDMED. “I’m looking for Al Gore,” he told me flat-out over lunch. Folks who know Petsko know the former Brandeis University biochemistry department chair isn’t one to mince words. And...