Amyloid Protein-Induced Remodeling of Morphometry and Nanomechanics in Human Platelets

Background/Objectives: The accumulation of specific amyloid proteins and peptides in the human brain is a hallmark of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Beyond the central nervous system, circulating peripheral blood cells are also exposed to these pathological proteins, which may contribute to the systemic disease manifestation. Human platelets (PLTs) were used as an in vitro model to investigate the impacts of amyloid Aβ1-42 peptide oligomers (Aβ42) and on-pathway α-synuclein (α-syn), two key amyloids implicated in AD and PD, on platelet biophysical properties. Methods: Using atomic force microscopy, imaging and force-distance modes, we analyzed changes in surface nanostructure, morphometric and nanomechanical signatures of PLTs, derived from healthy donors, following exposure to increasing concentrations of Aβ42 and α-syn. Results: Our findings show that platelet activation progresses with increasing amyloid concentration, characterized by cytoskeletal remodeling (filopodia-to-pseudopodia and lamellipodia transformation). While Aβ42 causes progressive decrease in the platelet membrane roughness, α-syn exhibits a biphasic effect-initial smoothing followed by a pronounced increase in the roughness at high concentrations. Both amyloids induce substantial increase in membrane stiffness (Young's modulus). Conclusions: The changes in PLTs' biophysical properties closely resemble the previously observed modification in PLTs derived from AD and PD patients, suggesting that amyloid proteins' interactions with PLTs may contribute to their dysfunction. Our results underscore the potential of platelets as peripheral indicators of neurodegeneration and point to their role in the systemic pathology of amyloid-associated diseases.