Fig. 1

Pathological features of the presymptomatic L315R 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 presymptomatic L315R case. The transentorhinal cortex (c) and other temporal regions showed age-related tau pathology (A0B2C0), appearing as Alzheimer-like argyrophilic neurofibrillary tangles (c1) and neuritic threads, but also Pick-body like inclusions (c2) characteristic of the L315R variant. The anterior temporal cortex (d) was characterized by milder age-related tau pathology (d1) and seldom a Pick body-like inclusion, but also astrocytic inclusions consistent with L315R pathology (d2). Similar ramified (e1) or punctate (f1) astrocytes were found in the middle frontal cortex (e) and amygdala (f), together with oligodendrocytic coiled bodies in the middle frontal white matter (e2) and Pick body-like inclusions (f2) in the amygdala. Scale overview = 200 μm; scale magnification = 20 μm

Legend: %AO = percentage of area occupied (by tau-positive pixels); 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; SUB = subiculum; TEC = transentorhinal cortex

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