FIGURE 1.

Histopathological lesions in Alzheimer’s disease (AD) brain. (A) Amyloid plaque stained using the BAM10 antibody (red channel), with associated dystrophic neurites (arrows), and nuclei stained with To-Pro (blue). (B–F) Evolution of the aggregation of the tau protein recognized by different antibodies directed against phosphorylated and truncated tau proteins. (B) Pre-neurofibrillary tangle (NFT) characterized by a diffuse granular staining in the neuronal soma (TauC-3, green channel; 423, red channel, arrows). Perinuclear immunoreactivity is observed. Lipofuscin is autofluorescent in the red channel (asterisk). (C) Small tangles (bead-like structures, arrows) visualized using two antibodies directed against the phosphorylated tau protein (pT231, green channel; CP13, red channel). (D,E) NFTs at different stages of aggregation. (D) NFT with a fibrillar structure in the form of a trabecula around the nucleus (arrows). (E) Compact NFT, where the PHFs have invaded the entire soma and displaced the nucleus from its original position, and visualised using pT231, which recognises a phospho-epitope within the mid domain (DA9). (F) Extracellular NFTs, the last stage of aggregation of the tau protein. In the neuronal soma, this structure is much looser, lacking a cell membrane and a nucleus. It consists of the minimum core of the filament (PHF core) and reacts with antibody 423, which recognizes truncation at Glu-391 (green channel) and phospho-tau S396 (red channel). Images obtained with a Leica SP8 confocal microscope.