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1. Interlaboratory Comparison of Assessments of Alzheimer Disease-Related Lesions: A Study of the BrainNet Europe Consortium

Author

David Meyronet, Isidro Ferrer, Nenad Bogdanovic, Herbert Budka, Manuel B. Graeber, Nicolas Kopp, Andy King, Maria Pikkarainen, Giorgio Giaccone, Ellen Gelpi, Irina Alafuzoff, Piero Parchi, Safa Al-Sarraj, Dietmar Rudolf Thal, Matthias Preusser, Rivka Ravid, Danielle Seilhean, Istvan Bodi, Hans A. Kretzschmar, Jean Jacques Hauw, Nathalie Streichenberger, Penelope Korkolopoulou, Jeanne E. Bell, Efstratios Patsouris, Thomas Arzberger, Wolfgang Roggendorf, Gabor G. Kovacs, Wouter Kamphorst, Orso Bugiani, Alafuzoff I., Pikkarainen M., Al-Sarraj S., Arzberger T., Bell J., Bodi I., Bogdanovic N., Budka H., Bugiani O., Ferrer I., Gelpi E., Giaccone G., Graeber M.B., Hauw J.J., Kamphorst W., King A., Kopp N., Korkolopoulou P., Kovacs G.G., Meyronet D., Parchi P., Patsouris E., Preusser M., Ravid R., Roggendorf W., Seilhean D., Streichenberger N., Thal D.R., and Kretzschmar H.

Subjects
Male, Silver Staining, Pathology, medicine.medical_specialty, Biopsy, Tau protein, Plaque, Amyloid, tau Proteins, Tissue Banks, Neuropathology, Beta-amyloid, Stain, Tissue microarray, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, Alzheimer Disease, Neuropathologic diagnosi, Humans, Medicine, Hyperphosphorylated tau, Registries, Senile plaques, Aged, Aged, 80 and over, Cerebral Cortex, Interlaboratory study, Amyloid beta-Peptides, Staining and Labeling, biology, business.industry, International Agencies, Neurofibrillary Tangles, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, Staining, Europe, Neurology, biology.protein, Female, Neurology (clinical), Alzheimer's disease, business
Abstract

This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)-the hallmark lesions of Alzheimer disease-and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Aβ) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Aβ (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease. Copyright © 2006 by the American Association of Neuropathologists, Inc.

Published
2006
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2. Inter-laboratory assessment of PrPSc typing in creutzfeldt-jakob disease: a Western blot study within the NeuroPrion Consortium

Author

Silvio Notari, Stéphane Haïk, Herbert Budka, Petra Weber, Thomas Ströbel, Lucia Limido, Hans A. Kretzschmar, Agustín Rodríguez, James W. Ironside, Isidre Ferrer, Fabrizio Tagliavini, Mark Head, Heinz Schimmel, Piero Parchi, Jean Jacques Hauw, Parchi P., Notari S., Weber P., Schimmel H., Budka H., Ferrer I., Haik S., Hauw J.J., Head M.W., Ironside J.W., Limido L., Rodriguez A., Strobel T., Tagliavini F., and Kretzschmar H.A.

Subjects
PrPSc Proteins, animal diseases, Blotting, Western, Disease, Computational biology, Creutzfeldt-Jakob Syndrome, Pathology and Forensic Medicine, Molecular typing, Western blot, medicine, Humans, Typing, Prion protein, Inter-laboratory, Research Articles, Brain Chemistry, medicine.diagnostic_test, business.industry, General Neuroscience, Strain typing, Laboratories, Hospital, Virology, nervous system diseases, Neurology (clinical), Spongiform encephalopathy, business
Abstract

Molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (TSEs). It relies on the detection of distinct protease-resistant prion protein (PrP Sc ) core fragments that differ in molecular mass and/or glycoform ratio. In this collaborative study, we tested the inter-laboratory agreement in TSE molecular typing. Sixteen characterized brain specimens from sporadic TSEs and variant Creutzfeldt-Jakob disease (vCJD) cases were distributed blindly to seven laboratories for molecular characterization by a defined protocol and classification. Agreement between laboratories in the classification of samples was excellent. In particular, there were no differences in the distinction between PrP Sc type 1, type 2A, and type 2B with one exception, which eventually was identified as a case with types 1 and 2 co-occurrence. This shows that the general technique and particular classification system used here are robust and represent a reliable basis for diagnostic and epidemiologic purposes. The subtle further distinction of subtypes among type 1 and type 2 groups requires high-sensitivity gel electrophoresis protocols that are unsuitable for routine diagnostic needs and must be reserved for research investigations. Further research is necessary on the identification and significance of co-occurrence of PrP Sc types 1 and 2 within one brain.

Published
2008

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