Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Estimation of pathological lesion stage from brain images.

Background: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a disease responsible for cognitive impairment in adult humans. It is caused by mutations in the colony stimulating factor 1 receptor gene (CSF1R) or alanyl-transfer (t) RNA synthetase 2 (AARS2) gene and affects brain white matter. Settlement of stages of the pathological brain lesions (Oyanagi et al.

Pathologic basis of the preferential thinning of thecorpus callosum in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Background: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an early onset dementia characterized by axonal loss in the cerebral white matter with swollen axons (spheroids). It had been reported that the preferential thinning and "focal lesions" of the corpus callosum were observed on T2-weighted MRI in ALSP patients. The present study aimed to reveal the pathologic basis of them in relation to brain lesion staging (I ~ IV: Oyanagi et al.

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum.

A family with hereditary diffuse leukoencephalopathy with spheroids caused by a novel c.2442+2T>C mutation in the CSF1R gene.

Clinical phenotypes of hereditary diffuse leukoencephalopathy with spheroids (HDLS), a familial progressive neurodegenerative disorder affecting the white matter of the brain, are heterogenous and may include behavioral and personality changes, memory impairment, parkinsonism, seizure, and spasticity. Thus, HDLS is frequently unrecognized and misdiagnosed. Heterozygous mutations located within the kinase domain of the gene encoding the colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor with key roles in development and innate immunity, have been shown in HDLS.

Prediction of Outcomes in Mild Cognitive Impairment by Using 18F-FDG-PET: A Multicenter Study.

Background: 18F-FDG-PET is defined as a biomarker of neuronal injury according to the revised National Institute on Aging–Alzheimer’s Association criteria.

Objective: The objective of this multicenter prospective cohort study was to examine the value of 18F-FDG-PET in predicting the development of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI).

Methods: In total, 114 patients with MCI at 9 participating institutions underwent clinical and neuropsychological examinations, MRI, and 18F-FDG-PET at baseline.

Inclusion body myositis coexisting with hypertrophic cardiomyopathy: an autopsy study.

Inclusion body myositis is an inflammatory myopathy characterized pathologically by rimmed vacuoles and the accumulation of amyloid-related proteins. Autopsy studies in these patients, including histochemical examinations of multiple skeletal muscles, have not yet been published. In this paper, we describe the autopsy findings of a patient with inclusion body myositis and hypertrophic cardiomyopathy.

[Yuasa-Mitsuyama disease].

Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases: Pick's disease with Pick bodies and frontotemporal lobar degeneration with tau-negative and ubiquitin-positive inclusions (FTLD-U). FTLD-U is now usually referred to as FTLD-TAR DNA binding protein 43 (TDP-43). FTLD-TDP-43, but not Pick's disease with tau-positive Pick bodies, is often associated with motor neuron disease (MND).

Treatment of behavioral and psychological symptoms of Alzheimer-type dementia with Yokukansan in clinical practice.

The efficacy and safety of the kampo medicine Yokukansan (YKS, TJ-54) in the treatment of behavioral and psychological symptoms of dementia (BPSD) were investigated in patients with Alzheimer's disease (AD) in an open-label study. This study included 26 patients who had been diagnosed as having AD and were not treated with donepezil hydrochloride. These patients were administered YKS (7.

Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease.

Yokukansan (YKS) is used frequently against behavioral and psychological symptoms of dementia (BPSD) together with donepezil in patients with Alzheimer's disease (AD). Here, we investigated the efficacy and safety of YKS in patients with AD in a non-blinded, randomized, parallel-group comparison study. Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory (NPI) subscales were enrolled in the study.

Clinical entity of frontotemporal dementia with motor neuron disease.

Non-Alzheimer-type dementias occur in association with a variety of pathological conditions that include a group of diseases characterized by atrophy of the frontal and temporal lobes. Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases: Pick's disease with Pick bodies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). The vast majority of FTLD-U is now referred to as FTLD-TDP, following the recent discovery of TAR DNA-binding protein of 43 kDa (TDP-43) as the major constituent of the ubiquitin-positive inclusions.

Changes in glucose metabolism due to aging and gender-related differences in the healthy human brain.

Using [(18)F]fluoro-deoxy-glucose-PET, we studied relative metabolic changes due to age- and gender-related differences in the brain of 126 healthy subjects from their twenties to seventies. We used a data-extraction technique, the three-dimensional stereotactic surface projections (3D-SSP) method, to measure metabolic changes with fewer effects of regional anatomic variances. Simple regression analysis revealed significant age-related increases in relative metabolic values in the parahippocampal and amygdala regions in both sexes in their twenties to forties, and significant age-related decreases in both sexes in their fifties to seventies.

EPR evidence of hydroxyl radical generation as an initiator of lipid peroxidation in amyloid beta-protein-stimulated PC12 cells.

Recent data from several groups suggest that the primary mechanism of amyloid beta-protein (Abeta) neurotoxicity may be mediated by free radicals. To evaluate this hypothesis, our aim is to make the mechanism of Abeta neurotoxicity clear, especially in the formation of free radicals. In this study, rat pheochromocytoma (PC12) cells were exposed to Abeta25-35 and confirmed free radical generations using two kinds of spin trap agents, 5,5-dimethyl-1-pyrroline-N-oxide; DMPO and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; POBN.

Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus.

Kainic acid (KA) induces seizures and degeneration in CA1 of the ventral hippocampus, though its mechanism of action is unknown. We used KA to induce seizures in freely moving rats prepared for in vivo microdialysis with probe placement, and then measured extracellular glutamate with an online fluorometric detector. Generation of free radicals was monitored by electron paramagnetic resonance (EPR) spectroscopy coupled with perfusion of the spin-trapping agent, alpha-(4-pyridyl- N-oxide)- N- tert-butylnitrone (POBN).

Expression of glutamate transporters and ionotropic glutamate receptors in GLAST knockout mice.

In order to investigate the molecular mechanism underlying high seizure susceptibility of GLAST knockout mice, we carried out Western blotting for the expression of GLT-1, EAAC-1, and several kinds of glutamate receptors in the hippocampus and the cortex. Although no significant difference was observed between GLAST (+/+) and (-/-) mice in terms of expression of GLT-1 and EAAC-1 in the hippocampus, these proteins were over-expressed in the frontal cortex in GLAST (-/-) mice (GLT-1, about 210% increase; EAAC-1, about 180% increase). Expression of hippocampal Glu-R1 and Glu-R2 in GLAST (-/-) mice was remarkably increased (Glu-R1, about 140% increase; Glu-R2, about 160% increase), while Glu-R3 and NMDA receptors levels (NMDA-R1, 2A and 2B) were equal to those in control.

Measurement of laminins in the cerebrospinal fluid obtained from patients with Alzheimer's disease and vascular dementia using a modified enzyme-linked immunosorbent assay.

We developed a new enzyme-linked immunosorbent assay (ELISA) system using antibodies against intact human laminin, laminin alpha(5)-chain, laminin beta(1)-chain, laminin gamma(1)-chain and laminin alpha(1)-chain peptide (YFQRYLI). Using this ELISA, we measured the anti-laminin immunoreactivity levels in the cerebrospinal fluid (CSF) obtained from patients with Alzheimer's disease (AD), vascular dementia (VaD), and other disorders. The present study showed the levels of certain laminins in CSF to demonstrate significant differences in the chain levels in different dementias.

Conditioned-fear stress increases Fos expression in monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei.

Many studies have demonstrated that physical or psychological stress can increase Fos expression in brainstem monoaminergic nuclei. Little is known, however, about the extent to which stress increases the expression of Fos in monoaminergic and nonmonoaminergic neurons in the brainstem. We examined the effects of conditioned-fear (CF) stress following mild footshock (FS) as unconditioned stress on Fos expression in the monoaminergic and GABAergic neurons of the ventral tegmental area (VTA), locus coeruleus (LC), and dorsal raphe nucleus (DR) in rats.

Nitric oxide and hydroxyl radicals initiate lipid peroxidation by NMDA receptor activation.

In this experiment, we used direct electron paramagnetic resonance (EPR) spectra to measure lipid peroxidation by hydroxyl radical (.OH), nitric oxide (.NO) and lipid radical (.

Morphological changes in immunopositive cells of ionotropic glutamate receptor subunits during the development of transplanted fetal ventral mesencephalic neurons.

To elucidate the morphological changes in immunopositive cells of ionotropic glutamate receptors within intrastriatal 'developing' grafts of fetal ventral mesencephalon (VM) in 6-hydroxydopamine-lesioned rats, immunohistochemistry was performed to detect cells expressing N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1), the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits (GluR1, GluR2/3, and GluR4), or tyrosine hydroxylase (TH) in the intrastriatal VM grafts at 1, 4, and 12 weeks following transplantation. One week after transplantation, TH-positive cells were detected without any immunoreactivity of the NMDA and AMPA receptor subunits in the grafts. Four weeks after transplantation, TH-positive cells, distributed homogeneously in the grafts, appeared to be multipolar and larger compared to those at 1 week post-grafting.