Direct Observations of Amyloid β Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of Aβ(1–40) and Aβ(1–42) Aggregation

• Autores: Esbjorner, Elin K.; Chan, Fiona T. S.; Rees, Eric; Erdelyi, Miklos; Luheshi, Leila; Bertoncini, Carlos Walter; Kaminski, Clemens F.; Dobson, Christopher M.; Kaminski Schierle, Gabriele S.
• Año de publicación: 2014
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Amyloid; Super-resolution fluorescence microscopy; Alzheimer; Fluorescence lifetime imaging
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Insight into how amyloid β (Aβ) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer’s disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of Aβ(1–40) and Aβ(1–42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of Aβ(1–42) aggregation are considerably faster than those of Aβ(1–40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how Aβ aggregation may occur within neurons.
Fil: Esbjorner, Elin K.. University Of Cambridge; Reino Unido. Chalmers University Of Technology; Suecia
Fil: Chan, Fiona T. S.. University Of Cambridge; Reino Unido
Fil: Rees, Eric. University Of Cambridge; Reino Unido
Fil: Erdelyi, Miklos. University Of Cambridge; Reino Unido
Fil: Luheshi, Leila. University Of Cambridge; Reino Unido
Fil: Bertoncini, Carlos Walter. Institute for Research in Biomedicine; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Kaminski, Clemens F.. University Of Cambridge; Reino Unido
Fil: Dobson, Christopher M.. University Of Cambridge; Reino Unido
Fil: Kaminski Schierle, Gabriele S.. University Of Cambridge; Reino Unido