Three-dimensional real time imaging of amyloid β aggregation on living cells

Alzheimer’s disease (AD) is a progressive disorder of the brain that gradually decreases thinking, memory, and language abilities. The aggregation process of amyloid β (Aβ) is a key step in the expression of its neurocytotoxicity and development of AD because Aβ aggregation and accumulation around neuronal cells induces cell death. However, the molecular mechanism underlying the neurocytotoxicity and cell death by Aβ aggregation has not been clearly elucidated. In this study, we successfully visualized real-time process of Aβ(42) aggregation around living cells by applying our established QD imaging method. 3D observations using confocal laser microscopy revealed that Aβ(42) preferentially started to aggregate at the region where membrane protrusions frequently formed. Furthermore, we found that inhibition of actin polymerization using cytochalasin D reduced aggregation of Aβ(42) on the cell surface. These results indicate that actin polymerization-dependent cell motility is responsible for the promotion of Aβ(42) aggregation at the cell periphery. 3D observation also revealed that the aggregates around the cell remained in that location even if cell death occurred, implying that amyloid plaques found in the AD brain grew from the debris of dead cells that accumulated Aβ(42) aggregates.