Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18051 Rostock, Germany
Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany
Semen Buvalyy
Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany
Jürgen Geisel
Institute for Clinical and Experimental Surgery, Saarland University, 66424 Homburg, Germany
Andreas Hermann
Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18051 Rostock, Germany
Dmitry A. Fedosov
Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany
Adrian Danek
Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, 81366 Munich, Germany
(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to misdiagnoses. (2) Methods: We measured the standard Westergren erythrocyte sedimentation rate (ESR) of various blood samples from NAS patients and healthy controls. Furthermore, we manipulated the ESR by swapping the erythrocytes and plasma of different individuals, as well as replacing plasma with dextran. These measurements were complemented by clinical laboratory data and single-cell adhesion force measurements. Additionally, we followed theoretical modeling approaches. (3) Results: We show that the acanthocyte sedimentation rate (ASR) with a two-hour read-out is significantly prolonged in chorea-acanthocytosis and McLeod syndrome without overlap compared to the ESR of the controls. Mechanistically, through modern colloidal physics, we show that acanthocyte aggregation and plasma fibrinogen levels slow down the sedimentation. Moreover, the inverse of ASR correlates with the number of acanthocytes (R2=0.61, p=0.004). (4) Conclusions: The ASR/ESR is a clear, robust and easily obtainable diagnostic marker. Independently of NASs, we also regard this study as a hallmark of the physical view of erythrocyte sedimentation by describing anticoagulated blood in stasis as a percolating gel, allowing the application of colloidal physics theory.
