Journal
BRAIN PATHOLOGY
Volume 18, Issue 4, Pages 484-496Publisher
WILEY
DOI: 10.1111/j.1750-3639.2008.00147.x
Keywords
Alzheimer's disease; immunohistochemistry; neurofibrillary pathology; neuropathological diagnosis; BrainNet Europe consortium
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Funding
- European Union grant FP6 [LSHM-CT2004-503039]
- MRC [G0600676] Funding Source: UKRI
- Medical Research Council [G0600676] Funding Source: researchfish
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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-mu m-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.
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