Fig. 3.

Neuropathological features in the anterior frontal cortex of the proband. There was mild superficial spongiosis (a), ballooned neurons were identified in H&E stained sections (b) and were confirmed by αB crystallin immunohistochemistry (c). A proportion of neurons contained basophilic inclusions (d). Tau-immunoreactive inclusions were abundant (e). High magnification revealed tau-positive dots and threads (f arrow and g arrow, respectively) and frequent neuronal inclusions with ring or crescent morphology (f), diffuse (g), flame-shaped (h) or globular appearance (j). In the subcortical white matter tau-immunoreactive oligodendroglial inclusions and threads were abundant (k). All inclusion types showed strong immunoreactivity for 4R tau isoforms (i), including structures resembling tufted astrocytes (m) and neuronal inclusions (n), while only a minority of inclusions could be identified using immunohistochemistry for 3R tau (l). There was strong immunoreactivity for p62 in a proportion of neuronal (o) and astrocytic inclusions (o inset). Many neuronal (p), astrocytic (q) and oligodendroglial inclusions (r) in addition to threads (r arrow) were argyrophilic as demonstrated using the Gallyas silver impregnation method. a, b, d H&E; c αB crystallin immunohistochemistry; e–k phospho-tau immunohistochemistry (AT8); i, m, n 4R tau immunohistochemistry; l 3R tau immunohistochemistry; o p62 immunohistochemistry; p–r Gallyas silver impregnation. Bar in a represents 100 μm in a, e; 50 μm in i, l; 25 μm in b, c, m–p; 10 μm in d, f–k, q, r