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

TLDR

Staging of Alzheimer’s disease neurofibrillary pathology requires distinguishing initial, intermediate, and late stages, and the original 1991 method used thick (100 µm) sections and silver staining to map tau deposition across brain regions. This study revises the staging protocol for routine laboratories by adapting tissue selection and processing to thin (5–15 µm) paraffin sections and incorporating a robust AT8 immunostain for hyperphosphorylated tau. The revised method employs automated processing of paraffin‑embedded sections with AT8 immunoreaction to detect hyperphosphorylated tau, enabling routine application. The authors anticipate that this protocol will allow more uniform application of the staging procedure.

Abstract

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 mum) 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 mum) 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.