Alterations in the red blood cell membrane proteome in alzheimer's subjects reflect disease-related changes and provide insight into altered cell morphology

The data suggest, (1) RBC shape/morphology changes in AD subjects are possibly attributed primarily to the changes (elevation or decrease) in the level of a series of membrane/cytoskeleton proteins involved in regulating the stability and elasticity of the RBC membrane, and (2) changes (elevation or decrease) in the level of a second series of proteins in the RBC membrane proteome reflect similar changes reported earlier by various investigators in AD or animal model of AD. Of particular interest, elevation of oxidative stress response proteins such as heat shock 90 kDa protein 1 alpha in AD subjects has been confirmed by western blot analysis in the RBC membrane proteome.The results suggest that this study provides a potential link between the alterations in RBC membrane proteome in AD subjects and AD pathology.Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by abnormal extracellular deposition of β-amyloid (Aβ) peptide and neuronal loss. Recently, we have analyzed red blood cell (RBC) morphology in blood from subjects with AD and reported [1] that > 15% of the RBCs are elongated as compared to 5.9% in normal controls (p < 0.0001). This observation suggests possible alterations in the RBC membrane architecture in AD subjects. These changes are likely to originate from modifications caused by Aβ interactions with RBCs [2,3] and/or changes in the expression level of certain RBC proteins.It is well established [4] that the cytoplasmic surface of the RBC plasma membrane contains a two-dimensional meshwork of proteins referred to as the spectrin membrane cytoskeleton. Attached to integral membrane proteins, this cytoskeleton provides elasticity, flexibility and stability to the RBC, as the cells continuously flow through the circulatory system. Passage through the narrow blood vessels and micro capillaries involve large changes in shear stress and significant deformation of the RBC. Because of the ease in obtaining RBCs and the lack of