posted on 2024-02-26, 18:05authored byVesa Halipi, Nima Sasanian, Julia Feng, Jing Hu, Quentin Lubart, David Bernson, Daniel van Leeuwen, Doryaneh Ahmadpour, Emma Sparr, Elin K. Esbjörner
Formation of amyloid-β (Aβ) fibrils is a
central pathogenic
feature of Alzheimer’s disease. Cell-secreted extracellular
vesicles (EVs) have been suggested as disease modulators, although
their exact roles and relations to Aβ pathology remain unclear.
We combined kinetics assays and biophysical analyses to explore how
small (<220 nm) EVs from neuronal and non-neuronal human cell lines
affected the aggregation of the disease-associated Aβ variant
Aβ(1–42) into amyloid fibrils. Using thioflavin-T monitored
kinetics and seeding assays, we found that EVs reduced Aβ(1–42)
aggregation by inhibiting fibril elongation. Morphological analyses
revealed this to result in the formation of short fibril fragments
with increased thicknesses and less apparent twists. We suggest that
EVs may have protective roles by reducing Aβ(1–42) amyloid
loads, but also note that the formation of small amyloid fragments
could be problematic from a neurotoxicity perspective. EVs may therefore
have double-edged roles in the regulation of Aβ pathology in
Alzheimer’s disease.