Lower Cranial Dystonia with Inflated Cheeks: A Case of Dystonic Respiratory Failure.

We herein report a 76-year-old woman who developed lower cranial dystonia with a peculiar appearance of cheek inflation. The patient showed strong contraction of the orbicularis oris muscles. Consequently, her cheeks were passively inflated by expiration without exit.

p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.

Background: The neuronal ceroid lipofuscinosis (NCL) are a group of autosomal recessive neurodegenerative disorders that are characterized by the accumulation of ceroid lipofuscins. The NCLs are categorized into four classes based on the age of onset. Kufs disease is a rare adult-onset NCL caused by mutations in the CLN6 gene, which is rarely observed in the Japanese population.

Spinocerebellar degeneration: Discrepancies between clinical and pathological diagnoses.

To improve the diagnostic accuracy of sporadic spinocerebellar degeneration (SCD), we assessed the clinical and pathological data of 1494 consecutive autopsy cases. The number of patients who received a diagnosis of sporadic SCD (including multiple system atrophy) either clinically or pathologically was 19 (1.3%).

Coexistence of Huntington's disease and amyotrophic lateral sclerosis: a clinicopathologic study.

We report a retrospective case series of four patients with genetically confirmed Huntington's disease (HD) and sporadic amyotrophic lateral sclerosis (ALS), examining the brain and spinal cord in two cases. Neuropathological assessment included a polyglutamine recruitment method to detect sites of active polyglutamine aggregation, and biochemical and immunohistochemical assessment of TDP-43 pathology. The clinical sequence of HD and ALS varied, with the onset of ALS occurring after the mid-50's in all cases.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomotor apraxia 1.

DNA single-strand breaks (SSBs) are non-overlapping discontinuities in strands ofa DNA duplex. Significant attention has been given on the DNA SSB repair (SSBR) system in neurons, because the impairment of the SSBR causes human neurodegenerative disorders, including early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also known as ataxia-oculomotor apraxia Type 1 (AOA1). EAOH/AOA1 is characterized by early-onset slowly progressive ataxia, ocular motor apraxia, peripheral neuropathy and hypoalbuminemia.

A neuropathological study of autosomal-dominant chorea-acanthocytosis with a mutation of VPS13A.

We report the first autopsy case of genetically confirmed, autosomal-dominant chorea-acanthocytosis (AD-ChAc), showing a heterozygous mutation (G-A) at nucleotide position 8,295 in exon 57 of VPS13A. The patient was a 36-year-old Japanese man and the duration of his illness was 11 years. Neuropathologically, the patient showed marked atrophy and neuronal loss, particularly small and medium-sized neurons, with astrocytic gliosis in the caudate nucleus, putamen and globus pallidus.

Development and characterization of a TAPIR-like mouse monoclonal antibody to amyloid-beta.

Tissue amyloid plaque immuno-reactive (TAPIR) antibody was better related to the effect of immunotherapy in Alzheimer's disease (AD) than ELISA antibody. Here we used a hybridoma technique to develop a TAPIR-like anti-human amyloid-beta (Abeta) mouse monoclonal antibody. The obtained monoclonal antibody, 3.

Autotaxin expression is enhanced in frontal cortex of Alzheimer-type dementia patients.

We searched for genes differentially expressed in the frontal cortices of Alzheimer-type dementia (ATD) patients compared with those of non-ATD controls using DNA microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. Here we show that the expression level of the autotaxin (also called lysophospholipase D or ecto-nucleotide pyrophosphatase/phosphodiesterase 2) gene was significantly greater in ATD cortices than in non-ATD cortices. In both ATD and non-ATD groups, the expression levels were greater in patients with the apoE epsilon3/epsilon4 genotype than in patients with the apoE epsilon3/epsilon3 genotype, although the differences were not statistically significant.

Wobble modification deficiency in mutant tRNAs in patients with mitochondrial diseases.

Point mutations in mitochondrial (mt) tRNA genes are associated with a variety of human mitochondrial diseases. We have shown previously that mt tRNA(Leu(UUR)) with a MELAS A3243G mutation and mt tRNA(Lys) with a MERRF A8344G mutation derived from HeLa background cybrid cells are deficient in normal taurine-containing modifications [taum(5)(s(2))U; 5-taurinomethyl-(2-thio)uridine] at the anticodon wobble position in both cases. The wobble modification deficiency results in defective translation.

Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer's disease.

The amyloid beta-protein (Abeta) ending at 42 plays a pivotal role in Alzheimer's disease (AD). We have reported previously that intracellular Abeta42 is associated with neuronal apoptosis in vitro and in vivo. Here, we show that intracellular Abeta42 directly activated the p53 promoter, resulting in p53-dependent apoptosis, and that intracellular Abeta40 had a similar but lesser effect.

Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression.

DNA microarrays with isotope labeling from gene-specific primers enable sensitive detection of rare mRNAs, including neurotrophin and cytokine mRNAs in the brain. Using high-quality RNA from postmortem brains, gene-expression profiles covering 1373 genes were assessed in the dorsoprefrontal cortex of schizophrenic patients and compared with those of nonpsychiatric subjects. Statistical analysis of the DNA microarray data confirmed the findings of a previous GeneChip study by Hakak et al.

Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease.

Previous studies have suggested that heparan sulfate proteoglycans (HSPGs) play a role in deposition of beta-amyloid protein (Abeta) in the Alzheimer's disease (AD) brain. In the present study, we demonstrated that glypican-1 can bind fibrillar Abeta, and the binding is mainly mediated by heparan sulfate (HS) chains. Further analysis revealed that glypican-1 is the major HSPG localized in detergent-insoluble glycosphingolipid-enriched (DIG) domains where all machineries for Abeta production exist and Abeta is accumulated as monomeric and oligomeric forms.

Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform.

A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients.

Interleukin-1 (IL-1) mediates psychological stress responses by regulating monoamine metabolism and secretion of corticotropin-releasing factor, and is therefore, implicated in various psychiatric diseases. To evaluate the contribution of IL-1 signaling to the brain pathology of schizophrenia, we measured protein and/or mRNA levels for IL-1beta and endogenous IL-1 receptor antagonist (IL-1RA) in the postmortem brain tissues of prefrontal and parietal cortex, putamen, and hypothalamus. Both protein and mRNA levels of IL-1RA were specifically decreased in the prefrontal cortex of schizophrenic patients, whereas IL-1beta levels were not significantly altered in all the regions examined.

Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.

Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients.

Brain hydrogen sulfide is severely decreased in Alzheimer's disease.

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals.