Comparison of two main fragmentation methods of amyloid beta fibrils for establishing an Alzheimer disease model in cell culture


Bahador Zırh E., Yazgı H., Akyel H., Tel B. C., Zırh S.

Acta Medica, vol.56, no.2, pp.92-107, 2025 (TRDizin)

  • Publication Type: Article / Article
  • Volume: 56 Issue: 2
  • Publication Date: 2025
  • Journal Name: Acta Medica
  • Journal Indexes: TR DİZİN (ULAKBİM)
  • Page Numbers: pp.92-107
  • Hacettepe University Affiliated: Yes

Abstract

Aim:  Amyloid  beta  fibrils  have  been  shown  to  play  a  role  in  plaque  formation  and  aggregation  in  Alzheimer’s  disease.  Obtaining  these  fibrils  using  two  main  methods  and  applying  them  to  Alzheimer’s  modelling  is  crucial  in  understanding  the  pathology  of  the  disease  at  the  molecular  level  and  identify  in  therapeutic  targets.  The  aim  of  our  study is to determine the optimum sonication parameters using probe and ultrasonic bath sonication laboratory methods and to demonstrate Alzheimer’s disease modelling at the cellular level. Methods:   Lyophilized   human   peptide   amyloid   beta1-42   fibrils   (fAβ1-42)  were  subjected  to  probe  sonication  for  1  minute  with  1,  3  and  5  second  on/off  pulse  applications  at  varying  ambient  temperatures  (room  temperature,  ice  and  ice  surrounded  by  dry  ice  [ISDI])  for  20,  40  and  60  cycles,  respectively.  Then,  ultrasonic  bath  sonication  was  performed  in  10  °C  water  for  1  hour.  The  length  of  the  fragmented  fibrils  was  quantified  by  transmission  electron  microscopy  (TEM).  fAβ1-42  at  different  concentrations  was  applied  to  SH-SY5Y  cell  line.  The  non-toxic dose and time of fAβ1-42 application were analysed using the WST-1  assay.  Intracellular  and  extracellular  fibrils  were  visualized  with  immunofluorescence (IF) labelling. Results:  Although,  fragmentation  was  observed  under  all  conditions,  it  was  observed  that  fibrillar  lengths  decreased  as  the  on/off  pulse  times   increased,   regardless   of   the   number   of   cycles   with   ice   and   dry  ice.  Additionally,  decreasing  the  temperature  increased  fibrillar  fragmentation. Conclusion: We anticipate that our study will contribute to the literature by  developing  an  effective  and  economical  sonication  method  for  fibrillar fragmentation with two main laboratory methods and obtaining fAβ1-42 that can be used in cells at optimum concentration.