[A 39 years old woman responding to modafinil with bilateral hypothalamic lesion associated with hyperthermia and hypersomnia: a case report].

A 39 years old woman was admitted to our hospital with a status epilepticus, with high fever of 41°C. Magnetic resonance Imaging (MRI) revealed high signal intensities of both sides of thalami and hypothalami in T2 weighted and fluid attenuated inversion recovery (FLAIR) images. A needle biopsy of the thalamic lesion was consistent with neuromyelitis optica spectrum disorder although her serum antibody to aquaporin-4 was negative.

Extensive cortical spongiform changes with cerebellar small amyloid plaques: the clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease.

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt-Jakob disease (sCJD). The patient was a 72-year-old woman who exhibited progressive dementia over the course of 22 months. Diffusion-weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage.

Sudden death in Parkinson's disease: a retrospective autopsy study.

The aim of this paper is to reveal the causes of death and to verify sudden death of Parkinson's disease (PD) in an autopsy study. We reviewed the clinical data and the causes of death in 16 PD patients who had postmortem examinations. Prior to autopsy, nine patients died of known causes: five patients died of aspiration pneumonia, two of myocardial infarction, one of asphyxia, and one of dilated cardiomyopathy.

Immunostaining of oxidized DJ-1 in human and mouse brains.

DJ-1, the product of a causative gene of a familial form of Parkinson disease, undergoes preferential oxidation of Cys106 (cysteine residue at position 106) under oxidative stress. Using specific monoclonal antibodies against Cys106 oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections from DJ-1 knockout and wild-type mice and in human brain sections from cases classified into different Lewy body stages of Parkinson disease and Parkinson disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in neuromelanin-containing neurons and neuron processes of the substantia nigra; Lewy bodies also showed oxDJ-1 immunoreactivity.

The FAM3 superfamily member ILEI ameliorates Alzheimer's disease-like pathology by destabilizing the penultimate amyloid-β precursor.

Accumulation of amyloid-β peptide (Aβ) in the brain underlies the pathogenesis of Alzheimer's disease (AD). Aβ is produced by β- and γ-secretase-mediated sequential proteolysis of amyloid-β precursor protein (APP). Here we identify a secretory protein named interleukin-like epithelial-mesenchymal transition inducer (ILEI, also known as FAM3 superfamily member C) as a negative regulator of Aβ production.

Regional analysis of striatal and cortical amyloid deposition in patients with Alzheimer's disease.

We aimed to analyse the detailed distribution pattern of amyloid-β (Aβ) in the striatum, and to examine whether there is any correlation between Aβ deposition levels in the striatum and cortical regions. Twenty patients with Alzheimer's disease underwent positron emission tomography using (11) C-Pittsburgh Compound B ((11) C-PiB) to quantify the Aβ deposition. Volumes-of-interest analyses were performed on the ventral striatum (VST), pre-commissural dorsal caudate (pre-DCA), post-commissural caudate (post-CA), pre-commissural dorsal putamen (pre-DPU), and post-commissural putamen (post-PU), followed by exploratory voxel-wise analyses.

Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene.

Objectives: Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective.

Alpha-synuclein immunohistochemistry of gastrointestinal and biliary surgical specimens for diagnosis of Lewy body disease.

In Lewy body disease, Lewy pathology (LP: the accumulation of α-synuclein in neuronal perikarya and processes as Lewy bodies and Lewy neurites and dots, respectively) is observed in the central and peripheral nervous systems. Previous autopsy or biopsy studies of individuals with Lewy body diseases (LBDs) indicated that LP could be observed in the peripheral nerves of the gastrointestinal (GI) systems. The aim of this study is to clarify whether examination of GI and biliary surgical specimens would be useful for diagnosing LBD.

Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al.

The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles.

Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy.

Imaging spectrum of sporadic cerebral amyloid angiopathy: multifaceted features of a single pathological condition.

Objectives: Sporadic cerebral amyloid angiopathy (CAA) is common cause of cerebrovascular disorders that predominantly affect elderly patients. When symptomatic, cortical-subcortical intracerebral haemorrhage (ICH) in the elderly is the most well-known manifestation of CAA. Furthermore, the clinical presentation varies from a sudden neurological deficit to seizures, transient symptoms and acute progressive cognitive decline.

Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan.

Objective: To investigate the clinical, genetic, and neuroradiologic presentations of idiopathic basal ganglia calcification (IBGC) in a nationwide study in Japan.

Methods: We documented clinical and neuroimaging data of a total of 69 subjects including 23 subjects from 10 families and 46 subjects in sporadic cases of IBGC in Japan. Mutational analysis of SLC20A2 was performed.

Influence of APOE genotype and the presence of Alzheimer's pathology on synaptic membrane lipids of human brains.

The APOE genotype is the major risk factor for Alzheimer's disease (AD); however, it remains unclarified how the ε4 allele accelerates whereas the ε2 allele suppresses AD development, compared with the more common ε3 allele. On the basis of the previous finding that the assembly of the amyloid-β protein (Aβ) into fibrils in the brain, an early and invariable pathological feature of AD, depends on the lipid environment, we determined the levels of synaptic membrane lipids in aged individuals of different APOE genotypes. In the comparison between amyloid-free ε2/ε3 and ε3/ε3 brains, the presence of the ε2 allele significantly decreased the level of cholesterol.

Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders.

To study the relationship between neurodegenerative diseases including argyrophilic grain disease (AGD) and late-onset schizophrenia and delusional disorders (LOSD; onset ≥40 years of age), we pathologically examined 23 patients with LOSD, 71 age-matched normal controls, and 22 psychiatric disease controls (11 depression, six personality disorder, two bipolar disorders, and three neurotic disorders cases). In all LOSD cases (compared to age-matched normal controls), the frequencies of Lewy body disease (LBD), AGD, and corticobasal degeneration (CBD) were 26.1 % (11.

Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer's disease brain.

Background: Intracytoplasmic inclusions composed of filamentous tau proteins are defining characteristics of neurodegenerative tauopathies, but it remains unclear why different tau isoforms accumulate in different diseases and how they induce abnormal filamentous structures and pathologies. Two tau isoform-specific antibodies, RD3 and RD4, are widely used for immunohistochemical and biochemical studies of tau species in diseased brains.

Results: Here, we show that extensive irreversible post-translational deamidation takes place at asparagine residue 279 (N279) in the RD4 epitope of tau in Alzheimer's disease (AD), but not corticobasal degeneration (CBD) or progressive supranuclear palsy (PSP), and this modification abrogates the immunoreactivity to RD4.

ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded.

Altered CpG methylation in sporadic Alzheimer's disease is associated with APP and MAPT dysregulation.

The hallmark of Alzheimer's disease (AD) pathology is an accumulation of amyloid β (Aβ) and phosphorylated tau, which are encoded by the amyloid precursor protein (APP) and microtubule-associated protein tau (MAPT) genes, respectively. Less than 5% of all AD cases are familial in nature, i.e.

Pathological features of FTLD-FUS in a Japanese population: analyses of nine cases.

We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease.

YY1 binds to α-synuclein 3'-flanking region SNP and stimulates antisense noncoding RNA expression.

α-synuclein (SNCA) is an established susceptibility gene for Parkinson's disease (PD), one of the most common human neurodegenerative disorders. Increased SNCA is considered to lead to PD and dementia with Lewy bodies. Four single-nucleotide polymorphisms (SNPs) in SNCA 3' region were prominently associated with PD among different ethnic groups.

The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis.

Background: A long non-coding RNA (lncRNA), nuclear-enriched abundant transcript 1_2 (NEAT1_2), constitutes nuclear bodies known as "paraspeckles". Mutations of RNA binding proteins, including TAR DNA-binding protein-43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS), have been described in amyotrophic lateral sclerosis (ALS). ALS is a devastating motor neuron disease, which progresses rapidly to a total loss of upper and lower motor neurons, with consciousness sustained.

Prion-like properties of pathological TDP-43 aggregates from diseased brains.

TDP-43 is the major component protein of ubiquitin-positive inclusions in brains of patients with frontotemporal lobar degeneration (FTLD-TDP) or amyotrophic lateral sclerosis (ALS). Here, we report the characterization of prion-like properties of aggregated TDP-43 prepared from diseased brains. When insoluble TDP-43 from ALS or FTLD-TDP brains was introduced as seeds into SH-SY5Y cells expressing TDP-43, phosphorylated and ubiquitinated TDP-43 was aggregated in a self-templating manner.

Differential expression of secreted phosphoprotein 1 in the motor cortex among primate species and during postnatal development and functional recovery.

We previously reported that secreted phosphoprotein 1 (SPP1) mRNA is expressed in neurons whose axons form the corticospinal tract (CST) of the rhesus macaque, but not in the corresponding neurons of the marmoset and rat. This suggests that SPP1 expression is involved in the functional or structural specialization of highly developed corticospinal systems in certain primate species. To further examine this hypothesis, we evaluated the expression of SPP1 mRNA in the motor cortex from three viewpoints: species differences, postnatal development, and functional/structural changes of the CST after a lesion of the lateral CST (l-CST) at the mid-cervical level.

Progressive apraxic agraphia with micrographia presenting as corticobasal syndrome showing extensive Pittsburgh compound B uptake.

A 65-year-old woman developed progressive apraxic agraphia, characterized by poorly formed graphemes, a kanji (Japanese morphograms) recall impairment, relatively preserved oral spelling of kanji characters, and incorrect stroke sequences on writing accompanied by micrographia over a 3-year period. She also showed minor degrees of rigidity, limb-kinetic apraxia, and ideomotor apraxia of the left hand. Although asymmetric rigidity and limb-kinetic apraxia strongly suggested corticobasal degeneration, (11)C-Pittsburgh compound B positron emission tomography (PiB-PET) showed the predominantly right-sided accumulation of amyloid β in the cortices and striatum.