Fig. 4

Phospho-tau Histopathology (Part I). a The TRE of case 1 (female, 55 years, NFT I, Table 1) displayed a few AT8-immunopositive neurons, but these were below the threshold for tau seeding (Fig. 3). With the exception of this case and case 3 (female, 50 years, NFT I, Table 1), the TRE of all 18 remaining individuals showed some degree of tau seeding activity (0.30–17.90, Fig. 3). b In case 16 (male, 58 years, NFT V, Table 1), moderate AT8 pathology (neuronal somata, axons) and low tau seeding (1.07) were detectable in the PG. c Punches mistakenly located in the dorsal raphe nucleus (DRN) of one individual (case 7, female, 93 years, NFT III, Table 1) showed AT8-immunoreactive neuronal pathology combined with mild tau seeding (0.79). d Some IO punches (case 7), with no AT8-positive cell bodies, contained isolated AT8-positive axons and low tau seeding activity (0.60). e Framed area in d at higher magnification. Arrows indicate two AT8-positive axons. f In the IO of case 7 (same individual as in c-e and g, h) we noted unexpected and marked aging-related tau astrogliopathy, ARTAG (example in the framed area). g, h A single AT8-positive neuron was seen in this punch from the GP accompanied by numerous AT8-immunoreactive axons (see also Fig. 5f), the latter possibly originating in the basal nucleus of Meynert (BN). Tau seeding in the GP of this case was moderate (2.65); notably, the BN of this individual also featured moderate tau seeding (5.46). I. The DN of case 9 (male, 72 years, NFT III, Table 1) had few AT8-positive cell bodies (pretangles) and was sub-threshold for tau seeding (0.25). In cases at NFT stages I and III, only one (case 12, female, 81 years, NFT III, Table 1) had mild tau seeding in this region (0.60). j, k Notably, in the CC of case 12 (female, 81 years, NFT III, Table 1), the Bergmann glia (here, as thorn-shaped astrocytes) and, in the molecular layer, their astrocytic processes were AT8-immunopositive and also had tau seeding (1.39). By contrast, the neurons in the Purkinje layer were AT8-negative and negative for tau seeding. Tau seeding (1.74) was detected in the CC of one additional individual (case 9, male, 72 years, NFT III, Table 1, Fig. 3)