Direct Observations of Amyloid beta Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of A beta(1-40) and A beta(1-42) Aggregation
Journal article, 2014

Insight into how amyloid beta (A beta) 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 A beta(1-40) and A beta(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 A beta(1-42) aggregation are considerably faster than those of A beta(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 A beta aggregation may occur within neurons.

FIBRILS

BRAIN

ACCUMULATION

OLIGOMERS

ALPHA-SYNUCLEIN

ALZHEIMERS-DISEASE

HUMAN

GROWTH

PROTEIN

INTRINSIC FLUORESCENCE

Biochemistry & Molecular Biology

PEPTIDE

Author

Elin Esbjörner Winters

Chemical Biology

F. Chan

University of Cambridge

E. Rees

University of Cambridge

M. Erdelyi

University of Cambridge

L. M. Luheshi

University of Cambridge

C. W. Bertoncini

IRB Barcelona - Institute for Research in Biomedicine

C. F. Kaminski

University of Cambridge

C. M. Dobson

University of Cambridge

G. S. K. Schierle

University of Cambridge

Chemistry and Biology

1074-5521 (ISSN)

Vol. 21 6 732-742

Subject Categories

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Organic Chemistry

DOI

10.1016/j.chembiol.2014.03.014

More information

Latest update

8/23/2021