Correlation of immunolabeled LM and EM images of Alzheimer disease (AD)-type pretangles. A mixture of granular tau immunoreactivity and tangle-like aggregates in a pretangle neuron from a normal aging brain (case 1) (A, stacked 3D image). This neuron was labeled with anti-tau antibody(AT8) visualized with QD 655, also labeled with Alexa 488 for clearer confocal images. When an EM section (C) and the corresponding LM counterpart on the same plane (B) were compared, the tangle-like aggregate (B, arrow; C, rectangle d) was found to be a small bundle of straight and paired helical filaments tightly arranged in parallel (D). Granular immunoreactivity on LM (C, rectangle e) corresponded to 15-nm straight filaments widely and randomly distributed throughout the cytoplasm on EM (E). Paired helical filaments were occasionally seen in pretangle neurons of AD (F). Another pretangle neuron with perinuclear accentuation of tau immunoreactivity (G, stacked 3D image; case 2). EM image (I) and the corresponding LM counterpart on the same plane (H) were compared, QD-decorated straight filaments were seen around the nucleus (N) and some of them were attached to the nuclear membrane at the tip (asterisk, J). Scale bars in A-C, G-I = 5μm; D, E, J = 500 nm; F = 100 nm.