Interrelationship between Changes in the Amyloid β 42/40 Ratio and Presenilin 1 Conformation.

ABSTRACT: The ratio of the longer (i.e., Aβ42/Aβ43) to shorter (i.e. Aβ40) species is a critical factor determining amyloid fibril formation, neurotoxicity and progression of the amyloid pathology in Alzheimer's disease. The relative levels of the different Aβ species are affected by activity and conformation of the γ-secretase complex catalytic component - presenilin 1 (PS1). The enzyme exists in a dynamic equilibrium of the conformational states, with so-called "close" conformation associated with the shift of the γ-secretase cleavage towards the production of longer, neurotoxic Aβ species. In the current study, fluorescence lifetime imaging microscopy, spectral Förster resonance energy transfer, calcium imaging and cytotoxicity assays were utilized to explore reciprocal link between the Aβ42 and

SUBMITTER: Zoltowska KM 

PROVIDER: S-EPMC5023509 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature