Fig. 5

Phospho-tau Histopathology (Part II). a A 4 mm punch from the IO of case 16 (male, 58 years, NFT V) included portions of the immediately adjacent intermediate zone (IRZ) with strongly AT8-positive neurons and axons. In the IO itself, a single AT8-immunoreactive axon was detectable and some perivascular ARTAG was present, but none of the neurons there were AT8-immunoreactive. Tau seeding was below threshold (0.24). In at least two additional individuals (cases 12 and 17), prominent AT8-positive neurons and axons in the IRZ accompanied by IO AT8-negative neurons as well as perivascular ARTAG may have accounted for the tau seeding signals in IO punches (2.29 and 4.74). b Framed area in a at higher magnification showing AT8-positive tau pathology at the punch edge. c A 3 mm punch with edges free of AT8 pathology from case 15 (female, 84 years, NFT V), in which no portions of the IRZ were included. d Framed area in c at higher magnification displaying a clean punch edge and, directly beyond it, AT8-positive pathology in the IRZ. Tau seeding activity in the IO of this case was below threshold (0.08). e AT8-positive axon (arrows) in the substantia nigra, pars compacta (SNpc) of case 13 (female, 88 years, NFT III). Some tau seeding in the SNpc was present in 13/20 individuals (0.81–14.20), and was exceeded in the lower brainstem only by 15/20 cases in the LC (1.00–19.43). f Arrows point to AT8-positive axons in the GP of case 7 (female, 93 years, NFT III) (see also Fig. 4g, h). g The highest propensity for tau seeding (33.77) was detected in the basolateral subnucleus of the amygdala (AMY) of case 18 (female, 76 years, Stage V), where severe diffuse neuronal AT8-pathology was accompanied by some AT8-immunopositive astrocytes (ARTAG). h, i Tau seeding activity in the LC first became more pronounced during NFT stages III and V, e.g., 11.96 in case 7 (female, 93 years, NFT III) (h); 19.43 in case 19 (male, 76 years, NFT III); and 5.71 in case 10 (male, 74 years, NFT III) in micrograph i. Arrow in i points to extraneuronal neuromelanin lying free in the neuropil after severe neuronal loss