Role of Red blood cells in vascular dysfunction-associated with alzheimer's disease

Aims Our attention is focused on the study of a new model based on the red blood cell (RBC) and on its interaction with Aß. RBC are highly deformable to assist blood flow in the microcirculation. For this reasons, abnormalities in RBC could contribute to Alzheimer's Disease (AD) by obstructing oxygen delivery to brain causing hypoxia. Method The cell aging was monitored morphologically and biochemically; the morphology was monitored using atomic force microscopy (AFM) imaging and measuring the RBC’ plasma membrane roughness employed as a morphological parameter capable to provide information on the structure and integrity of the membrane-skeleton. Results Upon injuries induced by Aß, RBC accelerate the aging and shorten their survival.Results evidence that Aß boosts the aging path and determines a faster development of crenatures and proto-spicules associated to an acceleration in the weakening of the cell-cytoskeleton contacts when acting simultaneously to additional stimuli such as the absence of glucose; on the other hand Aß alone, induces morphological effects that can be abolished by the presence of glucose. Biochemical data demonstrate that Aß dependent-morphological alterations occur contemporaneously to an activation of the signaling pathway triggered by acetylcholinesterase and caspase 3, involving protein kinase C isoforms and nitric oxide metabolism. Conclusion As a whole, our study provides a comprehensive picture in which Aß treatment of RBC induces changes in specific cell signalling events, in turns affecting the membrane–cytoskeleton interaction and the membrane integrity. Understanding these processes is highly relevant for the comprehension of the biochemical events which predispose to AD.