An autopsy report of three kindred in a Gerstmann-Sträussler-Scheinker disease P105L family with a special reference to prion protein, tau, and beta-amyloid.

Introduction: Gerstmann-Sträussler-Scheinker disease P105L (GSS105) is a rare variant of GSS caused by a point mutation of the prion protein (PrP) gene at codon 105 (proline to leucine substitution). It is clinically characterized by spastic paraparesis and dementia and histopathologically defined by PrP-plaques in the brain. This report describes a clinicopathological analysis of three autopsied kindred from a Japanese GSS105 family, plus a topological analysis of PrP, hyperphosphorylated tau (p-tau), and beta-amyloid (Aβ).

Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease.

Nasu-Hakola disease (NHD) is a form of presenile dementia associated with sclerosing leukoencephalopathy and polycystic lipomembranous osteodysplasia. This extremely rare inherited disease is caused by mutations in either DAP12 or TREM2. The present study was designed to assess the relationship between DAP12/TREM2 genotype, mRNA and protein expression levels by both Western blotting and immunohistochemistry, and the tissue distribution and pathomorphological phenotype of the microglia.

Lesions of cortical GABAergic interneurons and acetylcholine neurons in xeroderma pigmentosum group A.

Xeroderma pigmentosum (XP) is a rare genetic disorder caused by inherited disturbances in the nucleotide excision repair system; patients with XP groups A (XP-A), B, D, and G were shown to have progressive neurological disturbances. Particularly, XP-A patients, which account for approximately half of Japanese XP patients, show severe neurological disorders, including mental retardation and epilepsy. Herein, we performed an immunohistochemical analysis of the number of GABAergic interneurons (GABAis), including calbindin-D28K, parvalbumin, and calretinin, in the cerebral cortex and acetylcholinergic neurons (AchNs) in the nucleus basalis of Meynert (NM) and in the pedunculopontine tegmental nucleus (PPN) in six autopsy cases of XP-A in order to investigate the relationships between mental dysfunction and GABAis and AchNs.

Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue.

Mucopolysaccharidoses (MPS) are inherited disorders caused by the deficiency of lysosomal enzymes. Sanfilippo syndrome (MPS III) and Hunter syndrome (MPS II) are characterized by severe and mild neurological disorders, respectively, in which the neurodegenerative mechanisms remain to be clarified. We immunohistochemically examined the involvement of tauopathy/synucleinopathy, cell death and oxidative damage in the brains of three cases each of MPS IIIB and MPS II and age-matched controls.

Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy.

Dentatorubral-pallidoluysian atrophy (DRPLA) is one of the CAG-repeat diseases, and is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME) in addition to late adult type. We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD) in autopsy cases of DRPLA. Oxidative products to nucleosides, 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME.

Neuropathological analysis of the brainstem and cerebral cortex lesions on epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy.

In order to investigate epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy (DRPLA), we immunohistochemically examined the expression of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex in autopsy cases. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 cases of juvenile and 2 cases of early adult types with progressive myoclonus epilepsy (PME), 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to tyrosine hydroxylase, tryptophan hydroxylase, substance P, methionine-enkephalin, parvalbumin, calbindin-D28K, calretinin, and excitatory amino acid transporters.

Oxidative nucleotide damage and superoxide dismutase expression in the brains of xeroderma pigmentosum group A and Cockayne syndrome.

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are caused by a genetic defect of nucleotide excision repair mechanisms, showing cutaneous hypersensitivity to sunlight and progressive neurological disturbances. The cause of neurological abnormalities has yet to be clarified and fundamental treatments have never been established in both disorders. In order to investigate neurodegeneration of XPA and CS, we immunohistochemically examined deposition of oxidative stress-related materials of nucleotides and expression of two types of superoxide dismutase (SOD) in the brains from autopsy cases of XPA and CS.

Brainstem and basal ganglia lesions in xeroderma pigmentosum group A.

Xeroderma pigmentosum group A (XPA) is a hereditary disorder characterized by cutaneous symptoms and progressive neurodegeneration. Since XPA patients exhibit peripheral neuropathy, neuronal deafness, rigidity, dysphagia, and laryngeal dystonia, it is indispensable for investigation of the neurodegeneration to analyze brainstem and basal ganglia lesions clinically and pathologically; we have previously shown the role of oxidative stress in the development of basal ganglia lesions. Here we immunohistochemically examined the expression of neurotransmitters, calcium-binding proteins, and neuropeptides in the brainstem, basal ganglia, and thalamus in 5 XPA autopsy cases.