Fig. 4.

Pathology of proband 4. Amyloid pathology is shown by immunohistochemistry for amyoid beta protein in frontal cortex (a) and temporal cortex (b). Several different patterns of cortical amyloid deposition were seen including diffuse subpial, diffuse, and neuritic plaques and diffuse “clouds” in the entorhinal region. Severe and widespread cerebral amyloid angiopathy was present involving vessels in the spinal (c), cerebral (d), and cerebellar (e) meninges. Rare cerebellar amyloid plaques were noted. Tau pathology was widespread in the temporal cortex (g) mainly in the form of nonplaque neuritic deposition but also including plaque neurites and tangles. Plaque, tangle, and nonplaque neuritic tau deposition were found to affect the cerebral cortex in a wide distribution extending beyond the superior temporal gyrus and heavily involving the occipital cortex amounting to Braak stage VI. Tau staining was prominent in the substantia nigra (f) as both tangle and neuritic deposition. An unusual feature was strong focal glial tau deposition in the white matter in coils and fine neurites (not illustrated). Alpha synuclein staining showed no pathological deposition either in the cortex or subcortical regions including the substantia nigra (not illustrated).