Detecting beta-amyloid aggregation from time-resolved emission spectra

作者：Alghamdi A; Vyshemirsky V; Birch D J S; Rolinski O J^*

来源：Methods and Applications in Fluorescence, 2018, 6(2): 024002.

DOI：10.1088/2050-6120/aa9f95

• time-resolved emission spectra
• beta-amyloid
• protein aggregation
• dielectric relaxation

The aggregation of beta-amyloids is one of the key processes responsible for the development of Alzheimer's disease. Early molecular-level detection of beta-amyloid oligomers may help in early diagnosis and in the development of new intervention therapies. Our previous studies on the changes in beta-amyloid's single tyrosine intrinsic fluorescence response during aggregation demonstrated a four-exponential fluorescence intensity decay, and the ratio of the pre-exponential factors indicated the extent of the aggregation in the early stages of the process before the beta-sheets were formed. Here we present a complementary approach based on the time-resolved emission spectra (TRES) of amyloid's tyrosine excited at 279 nm and fluorescence in the window 240-450 nm. TRES have been used to demonstrate sturctural changes occuring on the nanosecond time scale after excitation which has significant advantages over using steady-state spectra. We demonstrate this by resolving the fluorescent species and revealing that beta-amyloid's monomers show very fast dielectric relaxation, and its oligomers display a substantial spectral shift due to dielectric relaxation, which gradually decreases when the oligomers become larger.

• 出版日期2018-4