Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry

By H. Braak, I. Alafuzoff, T. Arzberger, H. Kretzschmar, K. Del Tredici. Acta Neuropathologica, 2006

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Assessment of Alzheimer’s disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of AD-related neurofibrillary pathology originally described in 1991 was performed on unconventionally thick sections (100 μm) using a modern silver technique and reflected the progress of the disease process based chiefly on the topographic expansion of the lesions. To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections (5–15 μm) and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis. It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/e033c36427647b58fc63baad03d8b87bae602975

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Citations in the corpus

Primary age-related tauopathy (PART): a common pathology associated with human aging (2014, positive): “Braak stages [25, 27, 28].”
CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. (2006, methodology): “A staging system of Alzheimer’s-associated neurofibrillary pathology using immunohistochemistry and AT8 has been suggested (Braak et al., 2006).”
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease (2012, positive): “A note of caution is warranted concerning Braak NFT staging in non-AD tauopathies, as neuronal lesions in some of these diseases may be undetectable by common histochemical staining methods useful for AD neuropathologic change [98].”
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice (2011, background): “Most research has focused on NFTs because of the reported correlation between NFTs and disease progression in the brains of AD patients [8-10].”
PET Imaging of Tau Deposition in the Aging Human Brain (2016, neutral): “Further, by characterizing participants according to Braak stage, we also found, consistent with previous findings (Braak and Braak, 1991, 1997; Braak et al., 2006, 2011; Nelson et al., 2012; Serrano-Pozo et al., 2011), increasing Braak stage in cognitively healthy and diseased participants to be…”
The pathological process underlying Alzheimer’s disease in individuals under thirty (2011, methodology): “In its hyperphosphorylated state, the soluble tau protein tends to take on an abnormal configuration and undergoes aggregation into insoluble fibrillary material that appears as neuropil threads (NTs) in cellular processes and neurofibrillary tangles (NFTs) in neuronal somata [2, 7, 12, 20 , 41, 53”
National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2011, positive): “‘‘Intermediate’’ or ‘‘High’’ AD neuropathologic change (italicized) is considered sufficient explanation for dementia a NFT stage should be determined by the method of Braak [14, 15] b Ab/amyloid plaque score should be determined by the method of Thal et al.”
Classification and basic pathology of Alzheimer disease (2009, background): “AT8 was shown to be particularly robust in inter-laboratory assessment [4, 42].”