EJN：三种海洋海豚的阿尔茨海默病样神经病理

Immunolabelling (brown pigment) of phosphorylated tau protein (pTau) using antibody AT180 in the cerebral cortices of odontocetes. When at lower intensities, immunolabelling of pTau was present as cytoplasmic granules within the cell bodies of neurons (a), and with increased intensity of labelling, pTau frequently extended into the axons and dendrites (b,c). Irrespective of the intensity of cytoplasmic labelling, nuclei were consistently devoid of any labelling (c) although neurons that labelled intensely for pTau frequently contained pyknotic nuclei (d, arrowhead). Intensely phospho-tau-stained cells were found in animal (Gm5) and present in all sections of cerebral cortex available for examination (e,f). Neuritic plaques were present in both the white and grey matter in all four aged animals examined (Gm1, Gm5, La5 and Tt1) and within the grey matter often colocalized with neuropil threads (g, arrowhead). Similarly, neuritic plaques colocalized with phospho-tau-positive cell bodies (h,i, arrowheads). pTau labelling was present predominantly in cerebrocortical layers II and V (j). Positive control sections were composed of human brain tissue from a case of definitely diagnosed Alzheimer's disease (k). Semi-serial sections were used for the controls (k, positive; l, negative control)

Learning techniques used in Knowledge schoolsPhosphorylated tau (pTau) localized using antibody AT180 (brown pigment), in a young bottlenose dolphin (Tt2). pTau was present within neuropil of the white matter but not the grey matter (a). It was also present in the cytoplasm of nearly all neurons in the cerebrocortical grey matter but absent from the nuclei and surrounding neuropil (b). Furthermore, it was present within the neuropil of the white matter of the supralimbic/paralimbic/limbic lobes of the cortex and the cytoplasm of neurons contained within it (c). Greater magnification of cerebrocortical white matter highlighted the intense cytoplasmic labelling of neurons for pTau while sparing their nuclei (d)

GFAP (yellow), Iba1 (magenta) and Aβ fibril (cyan) immunofluorescence labelling in Globicephala melas (Gm1) (a–h), Lagenorhynchus albirostris (La5) (i–m) and Tursiops truncatus (Tt1) (n–u). Gm1 shows diffuse plaques (d,h), evidence of CAA (g, arrowhead) and localized presence of astrocyte processes near some (a, arrow) but not all (e) plaques. Microglia are located near to, but not within plaques (b,f). La5 shows extremely strong GFAP labelling (i), which bled through to other channels. Small diffuse plaques were present, including next to blood vessels (zoomed in section part label m, arrow) but no strong evidence of plaque-associated gliosis. Tt1 showed more punctate astrocyte labelling (n,r) with little association with plaques despite the presence of many diffuse (u) and the occasional dense-core (q) plaques. Although there was no association of microglia with the dense-core plaque (o), there were some microglial processes near the edge of a diffuse plaque (s). We confirmed dense-core plaques contained fibrils using Thioflavin S staining (v), which appeared in amyloid plaques stained for Aβ (w,x). Scale bars = 20 or 40 μm as indicated on panels

Immunohistochemical labelling (brown pigment) of astrocytes and microglia in grey and white matter from Globicephala melas (a–o), Lagenorhynchus albirostris (p–t) and Tursiops truncatus (u–y). All animals have both Aβ and pTau pathology as assessed by IHC, with the exception of Gm4 whose pTau status was not determined. Due to sample availability, different brain regions were assessed for each animal, with GFAP burden values are reported as % area of the image occupied by GFAP labelling. Graphs show an average ±SEM of 5 200 × 200 μm randomly selected regions of interest from both grey and white matter in each brain region (e,j,o,t,y). Iba1 labelling was fairly weak in all animals, although individual cells were resolvable in some sections, notably white matter from La5 (q) and Tt1 (v). GFAP labelling was clearer, with individual cells clearly resolvable in grey matter from Gm1 (c), Gm4 (h), Gm5 (m) and La5 (r). Tt1 showed a different pattern, with highly diffuse labelling in grey matter (w), but more readily resolvable cells in white matter (x), in contrast to the more punctate/mesh-like GFAP labelling in white matter from other animals (d,i,n,s). Iba1 and GFAP labelling seemed uniformly distributed through grey/white matter, with little evidence of gliosis as may be seen around neuritic plaques in human Alzheimer's disease brain. Data are shown as box plots with each individual animal mean as data points. Scale bars = 100 μm