Amyloid β42 oligomers induce neurotoxicity and pathogenesis of Alzheimer's disease
Deng Jiajun
Tao Qian
Liu Bin
Luo Yanyu
Zhu Yi
Yue Feng
Abstract：Objective To determine the neurotoxic effects of amyloid beta 42(Aβ42)oligomers and investigate the mechanism of their induction of Alzheimer's disease(AD)-like pathogenesis in neuronal cells.Methods Western blotting and transmission electron microscopy were used to identify the synthesized Aβ42 oligomers.In order to assess the impact of the oligomers,MTT assay was employed to measure cell viability in neuroblastoma cell line SH-SY5Y treated with 10μmol/L Aβ42 oligomers for 12 or 24 h,glutamatergic neurons derived from human embryonic stem cells(hESC)exposed to Aβ42 oligomers for 24,48,or 96 h,and corresponding control cells.TUNEL assay was utilized to assess the apoptosis of glutamatergic neurons.Additionally,immu-nofluorescence assay was applied to detect the changes in Aβ plaques and p-tau pathology.Results Western blotting displayed monomers and small-molecule aggregation(＜30 000)in our synthe-sized Aβ42 oligomers,and transmission electron microscopy showed that the synthesized oligomers were mainly in a shape of spherical particles.Treatment of 10 μmol/L Aβ42 oligomers for 12 and 24 h in SH-SY5Y cells significantly decreased cell viability when compared with the control cells[(70.89±2.54)％vs(100.00±2.02)％,(52.63±3.37)％vs(100.00±2.80)％,P＜0.05].The 10μmol/L oligomers treatment for 24,48 and 96 h also decreased cell viability in glutamatergic neu-rons(P＜0.05).The apoptotic rates was significantly higher in glutamatergic neurons after treat-ment for 48 and 96 h when compared to the control cells[(1.44±0.31)％vs(1.00±0.38)％,(1.75±0.64)％vs(1.00±0.31)％,P＜0.05].Furthermore,circular granular Aβ-positive plaque signals were observed in the glutamatergic neurons after treated with the oligomers for 24,48,and 96 h,but no such plaque signals were seen in the control cells.Additionally,glutamatergic neurons incu-bation with 10 μmol/L oligomers for 24 h resulted in tau hyperphosphorylation at the Thr231 site,with the average fluorescence intensity significantly higher than that in control cells(P＜0.05).Conclusion Aβ42 oligomers show toxic effects to both SH-SY5Y cells and glutamatergic neurons,and they can also induce glutamatergic neurons to produce AD pathology.
Keywords：Alzheimer diseaseamyloid beta-peptidesneuronsapoptosisamyloid β42 oligomers
Publication Date：2024-05-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 562-566 )