Digital pathology and image analysis for robust high-throughput quantitative assessment of Alzheimer disease neuropathologic changes

Janna Hackett Neltner, Erin Lynn Abner, Frederick A. Schmitt, Stephanie Kay Denison, Sonya Anderson, Ela Patel, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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 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 (R = 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 Î1/2m in apolipoprotein E [Latin Small Letter Open E]4 carriers vs 274.4 m 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.

Original languageEnglish
Pages (from-to)1075-1085
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Issue number12
StatePublished - Dec 2012


  • Alzheimer disease
  • Autopsy
  • Digital pathology
  • Image analysis
  • Neuropathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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