Journal of Alzheimer’s Disease 60 (2017) 845–857 DOI 10.3233/JAD-170363 IOS Press 845 Review Exploring Erythrocytes as Blood Biomarkers for Alzheimer’s Disease Anna Stevenson a,b , Dianne Lopez a , Paul Khoo a , Rajesh N. Kalaria a and Elizabeta B. Mukaetova-Ladinska a,* a Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK b The School of Life Sciences, University of Glasgow, University Avenue, Glasgow, UK Accepted 25 July 2017 Abstract. Peripheral biomarkers for dementia are few and far between. Despite research into blood plasma/serum biomarkers for dementia diagnostics, there is a lack of information on erythrocytes and their vast proteomes as potential biomarkers. This review identifies a number of relevant and potentially promising erythrocyte biomarkers for various subtypes of dementia. These include erythrocyte morphology, oxidative stress, and erythrocyte membrane proteins such as the glucose transporter (GLUT-1), amyloid-, IgG, Hsp90, calpain-1, and band 3 protein. Of those proteins identified Hsp90, amyloid-, calpain-1 and band 3 show the most promise as pre-clinical biomarkers. However, the most intriguing aspect of erythrocytes is their changed morphology in dementia. The altered morphology not only could be used as a diagnostic biomarker but may be crucial in early pathogenesis of the disease. Further work must be done to establish the pathological connection between the periphery and central disease processes. Keywords: Alzheimer’s disease, amyloid, erythrocyte, membrane, oxidative stress, protein INTRODUCTION The search for reliable blood biomarkers to diag- nose dementia has largely concentrated on the plasma or serum. A number of promising peripheral biomark- ers have been identified in plasma and serum, such as the inflammatory (IL6 and IL10) and trophic markers (proGNF and TNF-alpha), matrix metalloproteinases (MMP3 and MMP9) [1], amyloid- peptides [2], - 1-antitrypsin, -2-macroglobulin, apolipoprotein E, and complement C3 [3], but none of them have * Correspondence to: Elizabeta B. Mukaetova-Ladinska, Insti- tute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. E-mail: elizabeta.mukaetova-ladinska@newcastle.ac.uk. been taken forward for use in routine clinical set- tings. This is primarily due to the undefined origin of these markers and their inconsistent reproducibil- ity, the unreducible relationship with cognitive and non-cognitive dementia symptoms, as well as their unknown relationship to other age-associated dis- eases and associated pharmacological treatments. In contrast, identifying dementia biomarkers in blood cells somewhat lags behind, largely due to the labori- ous methodology to isolate certain blood cells and concentrating cellular proteins to measurable lev- els. The latter have been largely seen as potentially unpractical for development of user-friendly portable devices. Among blood cells, platelets have been extensively investigated [4–6], and a number of characteristic ISSN 1387-2877/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved