Hohberger, B. | Search bioRxiv

bioRxiv2022

Glaucoma and Alzheimer: Neurodegenerative disorders show an adrenergic dysbalance

Glaucoma disease is characterized by an increased intraocular pressure (IOP), glaucomatous alterations of the optic disc and corresponding visual field defects. Even lowering the main risk factor IOP until an individual target level does not prevent this neurodegenerative disorder from proceeding. Several autoimmune mechanisms were discovered, partly showing a functionality. One of these autoimmune phenomena targets the {beta}2 adrenergic receptor ({beta}2-AR; i.e. agonistic autoantibodies; {beta}2-agAAb) and is linked to the elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimers Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the {beta}2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against {beta}2-AR. In addition, different species of amyloid beta (A{beta}) monomers were tested (A{beta}1-14, A{beta}10-25, A{beta}10-37 A{beta}1-40, A{beta}1-42, A{beta}28-40, and [Pyr]-A{beta}3-42). Our results demonstrate that none of the short-chain A{beta} (A{beta}1-14, A{beta}10-25, or A{beta}28-40) showed any agonistic or inhibitory effect on {beta}2-AR. Contrary, long-chain [Pyr]-A{beta}3-42, representing a major neurogenic plaque component, exerted an activation that was blocked by the {beta}2-AR antagonist ICI118.551 indicating that the effect was realized via the {beta}2-AR. Moreover, the long chain A{beta}1-40, A{beta}1-42, and A{beta}10-37 yet not the short-chain A{beta} peptides prevented the clenbuterol induced desensitization of the {beta}2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the {beta}2-AR like the {beta}2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimers Disease, we postulate that overstimulation of the {beta}2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders.

neuroscience↗

bioRxiv2021

Physical phenotype of blood cells is altered in COVID-19

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than 4 million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in erythrocyte deformability, lymphocyte stiffness, monocyte size, and neutrophil size and deformability. While some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

biophysics↗