Fig. 2

Neuropathology. Overview (upper) Panel. Macroscopic aspect of the brain of individual I. (a, b) Coronal cut through the cerebral hemispheres (a, b), cerebellum (a) and brainstem (c, pons on the left, medulla oblongata on the right). Histology (lower) panel. Microscopic aspect of the brain of individual I. a Whole mounts of the cerebral hemispheres confirm the massive degree of global atrophy (a, haematoxylin and eosin, HE) and show paucity of myelin throughout the cerebral hemispheres and capsules (Kluver-PAS). b–e Photomicrographs of the cerebral cortex from the frontal lobe show loss of neurons, including pyramidal cells (b, HE; c, Nissl stain for nuclei), astrogliosis (d, glial fibrillary acidic protein, GFAP) and minimal degree of vascular proliferation (e, CD34). f, g Photomicrographs of the deep white matter adjacent to the lateral ventricles show loss of oligodendrocytes (f, HE) and moderate activation of microglia (IBA-1). h–j The more peripheral hemispheric white matter shows massive activation of microglia with ameboid morphology (h, IBA-1), lack of myelin (i, proteolipid protein stain for myelin) and loss of oligodendrocytes by apoptosis (j, CASP3 stain for apoptotic cells). k, l Photomicrographs of the basal ganglia (k, HE) and thalamus (l, Nissl) show loss of neurons and reactive gliosis. m, n In the cerebellum, microscopic examination shows loss of neurons in the granular and Purkinje cell layer (m, HE) and moderate reaction of the Bergmann glia (n, GFAP)