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Yoshio Tsuboi

Publications and source records attributed to Yoshio Tsuboi.

At least 19 recordsLinked to original sources
PubMed2006

Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau mutation).

The objective of this clinical-pathologic study was to identify biomarkers for a pallidopontonigral degeneration (PPND) kindred of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K tau mutation. Five affected subjects, one at-risk who later became symptomatic, and one at-risk asymptomatic mutation carrier, had abnormal (18)fluorodeoxyglucose PET demonstrating asymmetric temporal lobe hypometabolism. All except the asymptomatic mutation carrier had abnormal brain MRI. Parkinsonism, myoclonus, anosmia, insomnia, speech, and autonomic dysfunction were identified. Autopsy of six affected subjects showed frontotemporal degeneration with extensive tauopathy. Further studies of FTDP-17 patients are needed to replicate these findings.

Adult↗
PubMed2006

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative disorder, which has three cardinal features: behavioral and personality changes, cognitive impairment, and motor symptoms. FTDP-17 was defined during the International Consensus Conference in Ann Arbor, Michigan, in 1996. The prevalence and incidence remain unknown but FTDP-17 is an extremely rare condition. It is caused by mutations in the tau gene, which encodes a microtubule-binding protein. Over 100 families with 38 different mutations in the tau gene have been identified worldwide. The phenotype of FTDP-17 varies not only between families carrying different mutations but also between and within families carrying the same mutations. The pathogenetic mechanisms underlying the disorder are thought to be related to the altered proportion of tau isoforms or to the ability of tau to bind microtubules and to promote microtubule assembly. Definitive diagnosis of FTDP-17 requires a combination of characteristic clinical and pathological features and molecular genetic analysis. Genetic counseling should be offered to affected and at-risk individuals; for most subtypes, penetrance is incomplete. Currently, treatment for FTDP-17 is only symptomatic and supportive. The prognosis and rate of the disease's progression vary considerably among individual patients and genetic kindreds, ranging from life expectancies of several months to several years, and, in exceptional cases, as long as two decades.

Brain↗
PubMed2006

Effect of MAPT and APOE on prognosis of progressive supranuclear palsy.

To assess genetic influence on the clinical presentation of progressive supranuclear palsy (PSP), the genetic effect on disease course was examined for variants in the tau gene (MAPT) and the gene for apolipoprotein E (APOE) in 58 cases of pathologically confirmed PSP. Clinical indicators of disease course included age at symptomatic onset (AAO), age at death (AAD), and disease duration (DD) and the genetic effects examined included MAPT haplotypes and APOE genotypes. From linear regression analysis, the MAPT H1/H1 genotype was associated with significantly earlier AAO (P=0.038). The MAPT genotype did not significantly influence DD or AAD. The APOE epsilon4 allele did not significantly influence AAO, AAD, or DD. Male sex was a predictor for earlier AAO (P=0.015). The interaction between MAPT and APOE was not significant for AAD and DD, but a significant negative coefficient was found for AAO suggesting their combination does not have an additive effect. These results support the assertion that the H1/H1 genotype may contribute to the earlier occurrence of clinical symptoms.

Age of Onset↗
PubMed2006

Neuropathology of familial tauopathy.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a hereditary progressive neurodegenerative disorder. FTDP-17 was originally defined in Ann Arbor, Michigan, in 1996. Since then, more than 100 families with FTDP-17 have been described throughout the world, including 18 families identified in Japan. Genetic studies have identified 40 different mutations in the microtubule-associated protein tau (MAPT) gene. The clinical features of FTDP-17 are characterized by behavioral, cognitive and motor disturbances that may occur in various combinations and degrees. Neuropathologic examination shows that various degrees of atrophy may be present in the frontal and temporal lobes, basal ganglia, amygdala and hippocampus. All the brains from patients with FTDP-17 have also shown the presence of tau deposits in neurons and glial cells. Mutations in MAPT may result in the increased splicing of exon 10, leading to 4-repeat tau depositions in both neurons and glial cells. MAPT mutations outside of exon 10 show 3- and 4-repeat tau deposits, predominantly in neurons with less glial pathology. Neuronal pathology may resemble that of Alzheimer's disease or Pick's disease because of the presence of neurofibrillary tangles or Pick-like bodies, whereas glial pathology may resemble that of progressive supranuclear palsy or corticobasal degeneration because of the presence of coiled bodies, tufted astrocytes or astrocytic plaques. Correlations between genetic mutations and the heterogeneity of clinical and neuropathologic features remain unclear.

Adult↗
PubMed2006

[Serial MRI findings of intracranial tuberculomas: a case report and review of the literature].

Intracranial tuberculoma is an infectious disorder, occurring with or without tuberculous meningitis. Although intracranial tuberculoma is rare in developed countries, its frequency has increased in recent years in association with aging and immunocompromised hosts. Because of the low sensitivity of Mycobacterium tuberculosis cultures or of DNA detection from cerebrospinal fluid, diagnosis of intracranial tuberculoma is often difficult. Conventional magnetic resonance (MR) imaging of the tuberculoma yields variable results and is indistinct from other inflammatory lesions or brain tumors. We report the case of a 74-year-old woman with progressive neurologic deterioration. MR imaging of the brain showed multiple ring-like enhancing lesions in the supra- and infra-tentorial regions, mimicking multiple metastatic brain tumors. Diffusion-weighted imaging (DWI) of the brain showed homogeneous high signals in each lesion. A cavity in the lung suggested systemic involvement of tuberculosis. Despite extensive examination, tuberculosis could not be detected. Nevertheless, anti-tuberculosis treatment was administered. The patient's neurologic condition initially deteriorated for 4 weeks, then gradually improved. MRI showed marked improvement of the lesions after anti-tuberculosis treatment. Whereas conventional MRI is not specific in such cases, DWI might be useful for early assessment of intracranial tuberculosis.

Aged↗
PubMed2005

Diffusion-weighted MRI in familial Creutzfeldt-Jakob disease with the codon 200 mutation in the prion protein gene.

Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has been reported to be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). We report MRI findings with DWI, as well as with fluid-attenuated inversion recovery (FLAIR) and T1-weighted imaging (T1WI), in a case of familial CJD with a mutation at codon 200 of the prion protein gene. DWI in this patient showed high signal intensity in the basal ganglia and the cerebral cortex, similar to findings in sporadic CJD. In addition, T1WI showed areas of high signal intensity bilaterally in the globus pallidus. Despite the clinical diversity and atypical laboratory findings seen in familial CJD with the codon 200 mutation, these neuroimaging studies suggest that common regional distributions and a common pathogenesis might underlie the clinical progression both in sporadic CJD and in familial CJD with the codon 200 mutation in the prion protein gene. DWI abnormalities may be characteristic features that should be considered in the diagnosis of familial as well as of sporadic CJD.

Brain↗
PubMed2005

Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome.

The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD.

Aged↗
PubMed2005

Dementia with Lewy bodies and Parkinson's disease with dementia: are they different?

The relationship of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is debated. In DLB, dementia antedates Parkinsonism; in PDD, Parkinsonism antedates dementia. Other than presenting features, diagnostic measures fail to distinguish DLB from PDD. There are few or no pathologic differences between DLB and PDD. In most cases cortical Lewy bodies (LBs) are widespread and there is coexistent Alzheimer type pathology, insufficient to diagnose Alzheimer's disease. Given the predominance of Parkinsonism in PDD, neuronal loss in the substantia nigra is more severe in PDD than DLB. Further clinicopathologic studies are needed to define other pathologic differences between DLB and PDD and to explore the role of neuritic, basal forebrain and striatal pathology in these clinical syndromes.

Dementia↗
PubMed2005

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Adult↗
PubMed2005

[A case of pseudo Tolosa-Hunt syndrome with bacterial infection and literature review].

We report a case with recurrent orbital pain and unilateral cranial nerve paresis mimicking Tolosa-Hunt syndrome. However, these features were most likely caused by bacterial infection because of beneficial response to antibiotics therapy. A 32-year-old man developed severe right orbital pain and diplopia. Neurological examination revealed right oculomotor paresis and 1st division of the right trigeminal nerve dysfunction. MR imaging revealed thickness of right cavernous sinus region with marked gadolinium enhancement. Cerebrospinal fluid (CSF) examination was initially normal. Treatment with steroid showed marked improvement. However soon after tapering of steroid dosage, his symptoms recurred and deteriorated. He was referred to our hospital because of second opinion. Neurological examination still showed right oculomotor paresis and 1st division of the right trigeminal nerve dysfunction with orbital and retro-orbital pain. Re-examination of CSF showed pleocytosis with neutrocytes dominancy and elevated protein concentration. Intravenous treatment with penicillin was initiated with marked improvement. There have been reported cases with bacterial infection resulting pseudo Tolosa-Hunt syndrome, which have good response to antibiotics treatment with excellent prognosis. It is speculated that bacterial infection might cause clinical features mimicking Tolosa-Hunt syndrome in our case.

Adult↗
PubMed2004

CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation.

Molecular chaperones, ubiquitin ligases and proteasome impairment have been implicated in several neurodegenerative diseases, including Alzheimer's and Parkinson's disease, which are characterized by accumulation of abnormal protein aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau. CHIP also increases tau aggregation. Consistent with this observation, diverse of tau lesions in human postmortem tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show a significant reduction in tau levels. Together these data demonstrate that the Hsp70/CHIP chaperone system plays an important role in the regulation of tau turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target.

Animals↗
PubMed2004

Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration.

OBJECTIVES: To determine if apolipoprotein E epsilon 4 influences the frequency of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration and to determine if the frequency of Alzheimer-type pathologic features in synucleinopathies is similar to the frequency of such features in tauopathies and frontotemporal degeneration. METHODS: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and transitional Lewy body disease, frontotemporal degeneration, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, with a mean age of 75.1 +/- 9.3 years, were suitable for genetic and pathological analysis. Disorders were grouped as tauopathies (progressive supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body disease and multiple system atrophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of concomitant Alzheimer-type pathologic features in each case, and apolipoprotein E genotype was determined from DNA isolated from frozen brain tissue. The relationship of apolipoprotein E epsilon 4 to Alzheimer-type pathologic features was determined. RESULTS: Across all neurodegenerative disorders, apolipoprotein E epsilon 4 and older age independently predicted the co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degeneration), apolipoprotein E epsilon 4 had a similar effect, whereas older age and female sex were less predictive. There was a significant difference between the frequency of Alzheimer-type pathologic features in synucleinopathies and the frequency of such features in tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of apolipoprotein E epsilon 4 allele was not significantly different among the 3 groups. CONCLUSIONS: Apolipoprotein E epsilon 4, independent of older age and sex, contributes to the co-occurrence of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer-type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal degeneration.

Aged↗
PubMed2004

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.

Antiparkinson Agents↗
PubMed2004

[Garcin syndrome in a patient with rhinocerebral mucormycosis].

Garcin syndrome is characterized by an unilateral cranial nerves involvement without sensory or motor long-tract disturbances. It is usually caused by tumor infiltrating in the skull base with osteolytic changes on radiological study. We report a case of 64-year-old man with history of alcohol overintake, who admitted local hospital, because of right periorbital edema and facial swelling. He noted right ptosis 2 weeks prior to admission. Neurological examination revealed right multiple cranial nerves involvement including II, III, IV, V, and VI cranial nerves. MR imaging of the brain showed marked paranasal sinusitis and abnormal infiltration of right orbital fat. Orbital apex syndrome related to paranasal sinusitis was diagnosed, and antibiotics was administered. But a few days after admission, he developed a right VII, IX, X cranial nerve palsy. He was transferred to our hospital because of acute development of left hemiparesis and deteriorated consciousness. MR imaging of the brain showed right internal carotid artery (ICA) occlusion, and infarction in right middle cerebral artery (MCA)'s territory. The diagnostic biopsy of the paranasal sinus showed mucorales hyphae, indicating that the pathological diagnosis was mucormycosis. Despite of antibiotic therapy included of amphotericin-B administration and strict control of diabetic mellitus, his sinusitis was gradually spread. His condition progressively deteriorated, and finally died of sepsis. Post-mortem examination revealed a widespread mucor infiltration in the dura mater without skull bone invasion. This case presented with unilateral multiple cranial nerve involvements (Garcin syndrome) followed by left hemiparesis associated with rhinocerebral mucormycosis. It is suggested that mucormycosis should be considered in case of Garcin syndrome without osteolysis in the skull base.

Arterial Occlusive Diseases↗
PubMed2004

[Clinical, genetic and pathological aspects of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)].

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a group of hereditary, adult-onset, progressive neurodegenerative syndromes, which lead to the accumulation of intracellular deposits of hyperphosphorylated tau protein. Since the original definition of FTDP-17 in the Consensus Conference held in Ann Arbor, Michigan in 1996, it has become apparent that this syndrome has worldwide distribution. More than 80 families have been described in North America, Europe, Australia and Asia. The molecular genetic studies have identified 35 different mutations outside and on exon 10 of tau gene. The symptomatic onset of FTDP-17 is usually insidious. The clinical phenotypes are characterized by behavioral, cognitive and motor disturbances that may occur in various combinations and in varying degrees of severity. Affected individuals develop a constellation of signs, including at least two of the three cardinal manifestations of FTDP-17. It should be noted that there is significant clinical phenotypic heterogeneity in individuals with different mutations. In addition, interfamilial and intrafamilial variability of clinical phenotype is often seen among individuals carrying the same mutation. Macroscopically, the degree of brain atrophy observed varies with a brain weight ranging from approximately 825 to 1,290 grams. In the advanced stages, the degree of atrophy varies and may be present in the frontal and temporal lobes, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus and ventral hypothalamus. Microscopically, the neuropathologic hallmark is the presence of tau protein deposits in neurons or in both neurons and glia. The cellular pathology of the neuron may resemble that of Alzheimer disease (AD) or Pick disease for the presence of neurofibrillary tangles or Pick bodies. The cellular pathology of glial cells may resemble that of progressive supranuclear palsy or corticobasal degeneration for the presence of coiled bodies in oligodendroglial cells, tufted astrocytes or astrocytic plaques. Mutations in exons 1, 10 and intron following exon 10 are associated with neuronal and glial tau deposition. Mutations in exons 9, 11, 12 and 13 lead to deposits of tau filaments predominantly in neurons.

Adult↗