Validation of a Serum Screen for Alzheimer's Disease Across Assay Platforms, Species, and Tissues

Article type: Research Article

Authors: O'Bryant, Sid E.^{a; b; *} | Xiao, Guanghua^c | Zhang, Fan^d | Edwards, Melissa^e | German, Dwight C.^f | Yin, Xiangling^g | Como, Tori^{a; b} | Reisch, Joan^c | Huebinger, Ryan M.^h | Graff-Radford, Neillⁱ | Dickson, Dennis^{j; k} | Barber, Robert^{b; l} | Hall, James^{b; m} | O'Suilleabhain, Padraigⁿ | Grammas, Paula^g

Affiliations: [a] Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA | [b] Institute for Aging & Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA | [c] Department of Clinical Science, UT Southwestern Medical School, Dallas, TX, USA | [d] Department of Academic and Institutional Resources and Technology, University of North Texas Health Science Center, Fort Worth, TX, USA | [e] Department of Psychology, University of North Texas, Denton, TX, USA | [f] Department of Psychiatry, UT Southwestern Medical School, Dallas, TX, USA | [g] Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA | [h] Department of Surgery, UT Southwestern Medical School, Dallas, TX, USA | [i] Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA | [j] Department of Neuro-Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, USA | [k] Laboratory Medicine and Pathology, Mayo Clinic Jacksonville, Jacksonville, FL, USA | [l] Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA | [m] Department of Psychiatry, University of North Texas Health Science Center, Fort Worth, TX, USA | [n] Department of Neurology and Neurotherapeutics, UT Southwestern Medical School, Dallas, TX, USA

Correspondence: [*] Correspondence to: Sid E. O'Bryant, PhD, Health Science Center, Department of Internal Medicine, University of North Texas, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA. Tel.: +1 817 735 2961; E-mail: Sid.O'Bryant@unthsc.edu.

Abstract: Background:There is a significant need for rapid and cost-effective biomarkers of Alzheimer’s disease (AD) for advancement of clinical practice and therapeutic trials. Objective:The aim of the current study was to cross-validate our previously published serum-based algorithm on an independent assay platform as well as validate across tissues and species. Preliminary analyses were conducted to examine the utility in distinguishing AD from non-AD neurological disease (Parkinson’s disease, PD). Methods:Serum proteins from our previously published algorithm were quantified from 150 AD cases and 150 controls on the Meso Scale Discovery (MSD) platform. Serum samples were analyzed from 49 PD cases and compared to a random sample of 51 AD cases and 62 controls. Support vector machines (SVM) were used to discriminate PD versus AD versus controls. Human and AD mouse model microvessel images were quantified with HAMAMATSU imaging software. Mouse serum biomarkers were assayed via MSD. Results:Analysis of 21 serum proteins from 150 AD cases and 150 controls yielded an algorithm with sensitivity and specificity of 0.90 for correctly classifying AD. This multi-marker approach was then validated across species and tissue. Assay of the top proteins in human and AD mouse model brain microvessels correctly classified 90–100% of the samples. SVM analyses were highly accurate at distinguishing PD versus AD versus controls. Conclusions:This serum-based biomarker panel should be tested in a community-based setting to determine its utility as a first-line screen for AD and non-AD neurological diseases for primary care providers.

Keywords: Alzheimer's disease, blood-based biomarkers, serum, species, tissue

DOI: 10.3233/JAD-141041

Journal: Journal of Alzheimer's Disease, vol. 42, no. 4, pp. 1325-1335, 2014