Fig. 5

Effect of cholesterol content on APP processing and Aβ generation. APP is processed by β-secretase (BACE1) predominantly in cholesterol-rich lipid rafts. However, most of APP is localized outside rafts, and only a small fraction of APP is processed via the amyloidogenic pathway. An increase in cholesterol leads to increased raft organization, increased APP-BACE1 association within raft domains, and Aβ production (+ cholesterol). Another model suggests that lowering cholesterol levels may also promote amyloidogenesis (− cholesterol). Low cholesterol level leads to a lower number of rafts and lower amount of BACE1 in the rafts. As a result, BACE1 leaves the raft fraction and encounters its non-raft substrate, APP. Green circles, raft domain; yellow circles, non-raft area