Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Amyloid-β (Aβ) fibril formation is central to Alzheimer's disease pathogenesis.
• The role of extracellular vesicles (EVs) in modulating Aβ pathology is not fully understood.

Purpose of the Study:

• To investigate the effect of small extracellular vesicles (EVs) on the aggregation kinetics and fibril formation of Aβ(1-42).

Main Methods:

• Combined thioflavin-T monitored kinetics assays, seeding assays, and biophysical analyses.
• Utilized small (<220 nm) EVs from neuronal and non-neuronal human cell lines.
• Performed morphological analyses of Aβ(1-42) fibrils.

Main Results:

• EVs significantly reduced Aβ(1-42) aggregation by inhibiting fibril elongation.
• EVs led to the formation of shorter, thicker Aβ fibril fragments with less pronounced twists.
• EVs demonstrated a dose-dependent effect on Aβ aggregation.

Conclusions:

• EVs may play a protective role by reducing overall Aβ amyloid load.
• The formation of small amyloid fragments by EVs could pose neurotoxic risks.
• EVs exhibit a complex, potentially double-edged role in regulating Alzheimer's disease Aβ pathology.