title: Validation of a serum screen for Alzheimer's disease across assay platforms, species, and tissues.
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.
authors.affiliation: Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging & Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Sid E
authors.initials: SE
authors.lastname: O'Bryant
authors.affiliation: Department of Clinical Science, UT Southwestern Medical School, Dallas, TX, USA.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Academic and Institutional Resources and Technology, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Psychology, University of North Texas, Denton, TX, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Department of Psychiatry, UT Southwestern Medical School, Dallas, TX, USA.
authors.forename: Dwight C
authors.initials: DC
authors.lastname: German
authors.affiliation: Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging & Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Tori
authors.initials: T
authors.lastname: Como
authors.affiliation: Department of Clinical Science, UT Southwestern Medical School, Dallas, TX, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Reisch
authors.affiliation: Department of Surgery, UT Southwestern Medical School, Dallas, TX, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Huebinger
authors.affiliation: Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors.forename: Neill
authors.initials: N
authors.lastname: Graff-Radford
authors.affiliation: Department of Neuro-Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, USA Laboratory Medicine and Pathology, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dickson
authors.affiliation: Institute for Aging & Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Barber
authors.affiliation: Institute for Aging & Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA Department of Psychiatry, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hall
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical School, Dallas, TX, USA.
authors.forename: Padraig
authors.initials: P
authors.lastname: O'Suilleabhain
authors.affiliation: Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Grammas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008822:Mice, Transgenic; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood; D012372:ROC Curve; D012680:Sensitivity and Specificity; D060388:Support Vector Machine
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; blood-based biomarkers; serum; species; tissue