Fig. 1

Immunohistochemical findings. a, b pTau (clone AT8, 1:800 dilution) immunoreactivity concentrated at the depths of a cortical sulcus in the superior frontal cortex (Brodmann area 8). pTau is found in the soma and processes of both neurons and astrocytes in an irregular distribution concentrated around blood vessels: the defining lesion of CTE. The boxed area in (a) is represented at high power in (b). c pTau staining of anterior superior temporal lobe (Brodmann area 38), showing dense immunoreactivity of both neurons and astrocytes concentrated in superficial cortical layers (layers II-III). This superficial pTau is more evenly distributed throughout temporal cortex, with only occasional denser foci at sulcal depths (four foci across four blocks of anterior temporal lobe). pTau is also present in deeper cortical layers as irregular/patchy clumps of mixed neuronal and astrocytic staining. d Inferior temporal gyrus from another individual (77yo ex-ARF player with AD but no CTE), showing a pattern of pTau pathology distinct to that of CTE, with neuronal pTau staining concentrated in deeper cortical layers and dense neuritic staining.e Widespread pTau staining (as both globose tangles and pretangle pathology) in neurons of the substantia nigra, with accompanying neuritic pathology. There was accompanying moderate neuronal loss, pigment incontinence and gliosis. f pTDP-43 (clone 1D3, 1:500 dilution) staining of temporal lobe in the same superficial cortical layers depicted in (c), showing positive neuronal cytoplasmic inclusions and short neurites. g Beta-amyloid (betaA4 clone 6F/3D, 1:50 dilution) immunoreactivity in superior frontal cortex (Brodmann area 8). The boxed area is represented at high power in the inset. All immunohistochemistry performed on 4 μm sections from standard-sized blocks of formalin-fixed (10% neutral buffered formalin), paraffin-embedded tissue on a Leica BOND-MAX™ autostainer using the Leica BOND Polymer Refine detection system as per the manufacturer’s recommendations