Fig. 3

Pathological features of the early-stage G272V carrier

Figure portrays the severity of tau burden in grey matter and white matter regions (a), the severity of neuronal degeneration per region (b), and the morphology of neuropathological tau inclusions (c-f) in the early-stage G272V case. Moderate tau pathology was observed in frontotemporal neocortical and paralimbic regions, such as the subiculum (c), the superior frontal cortex (d), and the anterior temporal cortex (e). The striatum (f) was also moderately affected. Left-hemisphere regions were generally less affected than right-hemisphere regions (c; however, only hippocampus and middle frontal cortex were available from the right hemisphere), which was also consistent with evidence of right-lateralized atrophy from antemortem imaging (g). Tau pathology was predominantly neuronal, appearing as diffuse neuronal cytoplasmic inclusions (c1, f1), neurofibrillary tangle-like inclusions (c2), neuronal grains, and less often as Pick body-like inclusions (c2), ballooned neurons (d1) and perinuclear rings (e1). The white matter showed tiny diffuse threads and no intracellular oligodendrocytic pathology (c2). Scale overview = 200 μm; scale magnification = 20 μm

Legend: %AO = percentage of area occupied (by tau-positive pixels); ACC = anterior cingulate cortex; AMY = amygdala; ATC = anterior temporal cortex; CA1-4 = cornu ammonis 1–4; CAU = caudate nucleus; EC = entorhinal cortex; FG = fusiform gyrus; GD = gyrus dentatus; IPL = inferior parietal lobule; MFC = middle frontal cortex; PUT = putamen; SFC = superior frontal cortex; SUB = subiculum; TEC = transentorhinal cortex

Tau burden (y-axis, a) corresponds to the digitally measured %AO by tau pathology after applying natural logarithmic transformation