Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease

Abstract

Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer’s disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force–distance (FD) curves, which allowed us to retrieve the apparent Young’s modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology.

Label-Free Digital Holotomography Reveals Ibuprofen-Induced Morphological Changes to Red Blood Cells

“…In summary, the findings from our work highlight that the rheological properties of RBCs should be taken into account when formulating the safety levels for dose-dependent OTC and prescribed drug intake, particularly NSAIDs. We anticipate that our ML-based label-free imaging approach operable with the high spatial and temporal resolution even in resource-limited settings could be extended for the detection of pathologies that can adversely affect RBC morphology, such as in neurocognitive disorders ,, and transmissible diseases such as malaria …”

Acceleration of the Development of Microcirculation Embolism in the Brain due to Capillary Narrowing

“…29 Interestingly, the reduced deformability of RBCs is also found in patients with Alzheimer disease. 30 The normal size of RBCs is 7.3 µm and 5.8 µm in humans and mice, respectively. 31 If the capillary becomes narrower than this size, the flow resistance should increase, depending on the deformability of the RBCs.…”

Label-free digital holotomography reveals ibuprofen-induced morphological changes to red blood cells

“…In summary, the findings from our work highlight that the rheological properties of RBCs should be taken into account when formulating the safety levels for dose-dependent OTC and prescribed drugs intake, particularly NSAIDs. We anticipate that our ML-based label-free imaging approach operable with high spatial and temporal resolution even in resource-limited settings could be extended for detection of pathologies that can adversely affect RBC morphology, such as in neurocognitive disorders and transmissible diseases such as malaria (37, 49, 50).…”