Monoclonal antibody DC8E8 recognises developmental stages of Alzheimer’s disease tau neurodegeneration and Alzheimer’s disease–specific insoluble tau complexes. DC8E8 recognises preclinical Alzheimer’s disease (AD) (A), clinically incipient AD (B) and the fully developed final stage of AD (C). Hippocampal staining shows that DC8E8 detects early pretangle stages (D), intracellular neurofibrillary tangles (E) and extracellular neurofibrillary tangles (F). Tool bar: A-C 100 µm; D-F 10 µm. (G) DC8E8 recognizes soluble tau (lane 1) and sarkosyl-insoluble tau proteins (lane 2) in the material extracted from Braak stage VI AD brain tissue (allocortex tissue including hippocampus, entorhinal and temporal cortex). Western blot shows that DC8E8 detects AD-specific tau species with low and high molecular weights. For soluble tau (lane 1), 15 μg of total protein was loaded per lane. Sarkosyl-insoluble tau fraction (lane 2) was 50-fold enriched by solubilisation in a small volume of SDS-PAGE loading buffer (for details, see the Methods section).