title: Digital pathology and image analysis for robust high-throughput quantitative assessment of Alzheimer disease neuropathologic changes.
abstract: Quantitative neuropathologic methods provide information that is important for both research and clinical applications. The technologic advancement of digital pathology and image analysis offers new solutions to enable valid quantification of pathologic severity that is reproducible between raters regardless of experience. Using an Aperio ScanScope XT and its accompanying image analysis software, we designed algorithms for quantitation of amyloid and tau pathologies on 65 β-amyloid (6F/3D antibody) and 48 phospho-tau (PHF-1)-immunostained sections of human temporal neocortex. Quantitative digital pathologic data were compared with manual pathology counts. There were excellent correlations between manually counted and digitally analyzed neuropathologic parameters (R² = 0.56-0.72). Data were highly reproducible among 3 participants with varying degrees of expertise in neuropathology (intraclass correlation coefficient values, >0.910). Digital quantification also provided additional parameters, including average plaque area, which shows statistically significant differences when samples are stratified according to apolipoprotein E allele status (average plaque area, 380.9 μm² in apolipoprotein E [Latin Small Letter Open E]4 carriers vs 274.4 μm² for noncarriers; p < 0.001). Thus, digital pathology offers a rigorous and reproducible method for quantifying Alzheimer disease neuropathologic changes and may provide additional insights into morphologic characteristics that were previously more challenging to assess because of technical limitations.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kentucky, 800 Rose St, MS-115A, Lexington, KY 40536, USA. jmhack0@uky.edu
authors.forename: Janna Hackett
authors.initials: JH
authors.lastname: Neltner
authors.forename: Erin Lynn
authors.initials: EL
authors.lastname: Abner
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.forename: Stephanie Kay
authors.initials: SK
authors.lastname: Denison
authors.forename: Sonya
authors.initials: S
authors.lastname: Anderson
authors.forename: Ela
authors.initials: E
authors.lastname: Patel
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012044:Regression Analysis; D012720:Severity of Illness Index; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins