Open Access

Irina Alafuzoff, Thomas Arzberger, Safa Al-Sarraj, Istvan Bodi, Nenad Bogdanovic, Heiko Braak, Orso Bugiani, Kelly Del Tredici, Isidro Ferrer, Ellen Gelpi, Giorgio Giaccone, Manuel B. Graeber, Paul Ince, Wouter Kamphorst, Andrew King, Penelope Korkolopoulou, Gábor G. Kovács, Sergey Larionov, David Meyronet, Camelia Monoranu, Piero Parchi, Efstratios Patsouris, Wolfgang Roggendorf, Danielle Seilhean, Fabrizio Tagliavini, Christine Stadelmann, Nathalie Streichenberger, Dietmar R. Thal, Stephen B. Wharton, Hans Kretzschmar

• It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.