Biomedical subjects

Yoshio Hashizume

Publications and source records attributed to Yoshio Hashizume.

At least 19 recordsLinked to original sources

PubMed2006

Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation.

INTRODUCTION: Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. METHODS: We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. RESULTS: Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. CONCLUSION: We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness.

Adenocarcinoma, Papillary↗

PubMed2006

Recurrent limbic and extralimbic encephalitis associated with thymoma.

A 33-year-old woman, with a 7-year clinical history of invasive thymoma treated at ages 26 and 30 years by thymectomy and radiation, presented with a generalized convulsion and loss of consciousness. Following the seizure there was no neurological deficit and normal tendon reflexes. Magnetic resonance imaging (MRI) of the brain without gadolinium enhancement revealed multiple small lesions of high signal intensity on T2 and diffusion weighted images located in the cortical area beyond the temporal lobes. Brain biopsy demonstrated encephalitis with activated microglias and activated T-cell infiltration. Within 4 months of treatment with nothing other than anticonvulsant therapy, the lesions visible on the original MRI had completely disappeared and the patient was discharged with no neurological symptoms. The patient subsequently had two more episodes with a variety of symptoms such as incontinence, confusion, aphasia, apallial syndrome, and motor paresis. MRI following these episodes again revealed multiple lesions of similar appearance to those of the first episode, although in different locations, and much larger and more numerous. The patient had steroid pulse therapy after both episodes and the lesions noted on brain MRI disappeared within a few months with minimal neurological complications.

Administration, Oral↗

PubMed2006

TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS). Using biochemical and immunohistochemical analyses, we have identified a TAR DNA-binding protein of 43 kDa (TDP-43), a nuclear factor that functions in regulating transcription and alternative splicing, as a component of these structures in FTLD. Furthermore, skein-like inclusions, neuronal intranuclear inclusions, and glial inclusions in the spinal cord of ALS patients are also positive for TDP-43. Dephosphorylation treatment of the sarkosyl insoluble fraction has shown that abnormal phosphorylation takes place in accumulated TDP-43. The common occurrence of intracellular accumulations of TDP-43 supports the hypothesis that these disorders represent a clinicopathological entity of a single disease, and suggests that they can be newly classified as a proteinopathy of TDP-43.

Aged↗

PubMed2006

MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical pathology.

We report an autopsy case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) with widespread cerebral neocortical pathology. Initial symptoms were progressive insomnia and mental disturbance. Magnetic resonance imaging revealed no high-signal intensity lesions on diffusion-weighted images and later showed gradually progressive cerebral atrophy. Periodic synchronous discharges and myoclonus were not observed. Upon neuropathologic examination, widespread cerebral neocortical involvement with fine vacuole-type spongiform change was observed. Severe degeneration with almost complete neuronal loss, tissue rarefaction, numerous fat-laden macrophages and hypertrophic astrocytosis of the medial thalamic nucleus was evident. The inferior olivary nucleus showed severe involvement with neuronal loss and hypertrophic astrocytosis. In the cerebellar cortex, moderate depletion of Purkinje neurons was evident, with no spongiform change in the molecular layer and no neuronal loss in the granule cell layer. Immunohistochemistry for prion protein (PrP) revealed widespread synaptic-type deposits with some primitive plaque-type deposits in the cerebral neocortex, basal ganglia and cerebellar cortex. PrP deposition was also observed in the brainstem, particularly the tegmentum, substantia nigra and pontine nucleus, and spinal cord, particularly the posterior horn. In the medial thalamus and inferior olivary nucleus, PrP deposition was sparse. Analysis of the PrP gene showed no mutation but did show methionine homozygosity at polymorphic codon 129. Western blot analysis of protease-resistant PrP indicated the presence of type 2 PrP. We believe that this patient suffered from MM2-thalamic-type sCJD (sporadic fatal insomnia) with widespread cerebral neocortical pathology due to prolonged disease duration. The present case showed different patterns of spongiform degeneration and PrP deposition in the cerebral neocortex than those in previously reported MM2-thalamic-type sCJD cases.

Adult↗

PubMed2006

Clinicopathologic characteristics of sporadic Japanese Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type.

We analyzed neuropathologic features of 23 Japanese patients with sporadic Creutzfeldt-Jakob disease (sCJD) by means of prion protein (PrP) immunolabeling associated with codon 129 polymorphism of the PrP gene and western blot analysis of protease-resistant PrP (PrP type). Clinical features, particularly age at onset, disease duration, periodic synchronous discharge and presence of myoclonus, were also analyzed. This study included 11 cases of subacute spongiform encephalopathy (SSE), 10 cases of panencephalopathic (PE)-type sCJD and two cases of thalamic-type sCJD, classified according to cerebral pathology findings. According to PrP gene polymorphism and PrP type, 18 cases were classified as MM1-type, two as MV1-type, two as MM2-type and one as MM1 + 2-type sCJD. SSE and PE-type sCJD showed similar clinical features, with the exception of disease duration, codon 129 polymorphism and PrP type. Thalamic-type sCJD showed different clinical features and PrP type. We suggest that SSE and PE-type sCJD comprise the sCJD subtype and that PE-type sCJD is a prolonged pathologic phenotype of SSE. When we compare our results with those from a series of Caucasian sCJD patients, the percentages of codon 129 polymorphisms differed, as did classification based on PrP gene polymorphism and PrP type; our series included many PE-type sCJD cases and disease duration was relatively long and MM2-type cases showed clinicopathologic variability.

Adult↗

PubMed2006

Argyrophilic grain disease: frequency and neuropathology in centenarians.

Argyrophilic grain disease (AGD) is a progressive degenerative disease of the human brain, the prevalence of which increases with advancing age. The features of AGD in autopsied brains from 32 centenarians were studied using phosphorylated tau (AT8) immunostaining combined with Gallyas-Braak staining and 4R tau-specific antibody (RD4) immunostaining. Ten of 32 centenarians were diagnosed as AGD, yielding an overall frequency of 31.3%. In the demented group, nine (39.1%) of 23 cases were found with argyrophilic grains (AGs), while in the non-demented group, AGs were found in only one (11.1%) of nine cases, the difference between them being significant (P<0.05). Among the cases with Alzheimer's disease (AD), five (41.7%) of 12 were found with AGs. One (25%) of four cases with senile dementia with tangles (SDT) also suffered from AGD. Dementia caused by "pure" AGD accounted for 13% (3/23) among demented subjects. Our findings indicated that there is a high frequency of AGD in centenarians. In agreement with previous studies, we favor the view that age may be one of the risk factors for AGD.

Aged, 80 and over↗

PubMed2006

Characteristics of alpha-synucleinopathy in centenarians.

To investigate the characteristics of alpha-synucleinopathy in the brains of centenarians, the autopsied brains and spinal cords from 23 cases were studied. Coronal slices were prepared from a section of the cerebral hemisphere, following the guidelines of the Consortium to Establish a Registry for Alzheimer's Disease (AD) (CERAD) and the consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB). Spinal cord specimens were prepared at each segment from the third cervical to the third sacral segment. In all cases, we performed standard stainings of hematoxylin-eosin, Klüver-Barrera, and Gallyas-Braak combined with Luxol fast blue/cresyl violet, and alpha-synuclein (AS), phosphorylated tau (AT8) and beta-amyloid protein immunostainings. One-way ANOVA analysis, Chi-square or Fisher exact test were used for statistical analysis. Overall, AS-positive structures were found in 8 (34.8%) of our 23 centenarians, 6 (35.3%) of 17 demented patients, and four (40%) out of ten AD patients. The frequencies of AS lesions in the brains with senile plaque (SP) stage 0-A, B, and C were 27.7, 33, and 50%, respectively. No statistical differences were found among the frequencies of AS lesions in the subgroups of NFT stages I-II, III-IV, and V-VI (P=0.478). Most cases showed a widespread distribution of AS-positive structures except for one patient, in whose brain only the medulla was involved. The distribution pattern of AS-positive lesions was similar to that in Parkinson's disease or DLB, but the pigmented neurons in substantia nigra were relatively well preserved. Our findings indicate that there is a high frequency of alpha-synucleinopathy in centenarians, SP-positive and AS-positive lesions may involve a synergistic interaction.

Aged, 80 and over↗

PubMed2006

Acute motor and sensory neuronopathy associated with small-cell lung cancer: a clinicopathological study.

A 48-year-old Chinese woman developed ascending motor paralysis while visiting Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient's course was complicated by anoxic encephalopathy. Nerve conduction studies revealed a severely decreased amplitude of compound muscle action potentials and a sural nerve biopsy specimen showed findings consistent with axonal-form Guillain-Barr6 syndrome. An autopsy, excluding the brain, demonstrated small-cell lung cancer that was not detected clinically, axonal-dominant degeneration in the nerve roots and distal peripheral nerves, and the loss of both myelin and axons in the dorsal spinal column. The spinal anterior horn cells were severely decreased and were accompanied by astrocytic reaction in all spinal segments with lymphocytic infiltration. A limited examination of the dorsal root ganglia did not show Nageotte nodules, but the infiltration of T cells was observed. Although the clinical course mimicked axonal-form Guillain-Barré syndrome, the autopsy demonstrated both sensory and motor neuronal involvement, as well as small-cell lung cancer. Although anti-Hu and antiganglioside antibodies were negative in the patient's serum, the para-neoplastic mechanism might have damaged the anterior horn and dorsal root ganglia cells, which subsequently led to secondary axonal degeneration. There has been a report on a case of paraneoplastic subacute motor neuronopathy, but the acute course described here has not been reported before.

Carcinoma, Small Cell↗

PubMed2006

Autopsy case of sporadic Creutzfeldt-Jakob disease presenting with signs suggestive of brainstem and spinal cord involvement.

We describe an autopsy case of MM1-type sporadic Creutzfeldt-Jakob disease (CJD), the duration of which was 93 days. The patient was a 59-year-old Japanese man with no family history of prion disease or known iatrogenic exposure to CJD. His first symptom was dysesthesia in the left arm, suggestive of cervical cord involvement, and he showed rapidly progressive neurologic signs, such as dysarthria, dysphagia, lethargy, sleep apnea and respiratory failure, suggestive of brainstem involvement. Progressive mental deterioration combined with episodes of myoclonic seizure and periodic synchronous discharges on the electroencephalogram were observed in the later disease stage. Autopsy showed typical spongiform change to be wide-spread in the cerebral and cerebellar cortices, thalamus and basal ganglia. Synaptic-type PrP deposition was marked in the cerebral cortex, thalamus and basal ganglia. In the cerebellum, although the granular, molecular and Purkinje cell layers were well preserved from neuronal loss and gliosis, PrP deposition was marked in the molecular and granular cell layers. Spongiform degeneration and neuronal loss were not seen in the brainstem and spinal cord, but relatively marked PrP deposition was observed in the quadrigeminal body, substantia nigra, pontine nucleus, inferior olivary nucleus and posterior horn. Immunohistochemical staining for HLA-DR showed proliferation of activated microglia in the cerebral and cerebellar cortices, pontine nucleus, inferior olivary nucleus and posterior horn. The mechanisms underlying the neurologic symptoms and signs were unclear, but we speculate that, in addition to widespread involvement of the cerebral cortex, PrP deposition and microglial activation in the brainstem and spinal cord were responsible.

Brain Stem↗

PubMed2006

[An autopsy case of long-course multiple system atrophy (MSA) with remarkable atrophy and numerous NCI in the temporal lobe].

The patient was 66 year-old man with no family history of neurological diseases. At age 51, he showed initial symptom of parkinsonism, and was revealed a cerebellar atrophy by CT at age 52. He was suffered from malignant syndrome followed by renal dysfunction, which needed hemodialysis therapy. At age 54, he admitted to our hospital, when he showed parkinsonism, ataxia and dysautonomia. Neuroimaging study disclosed typical findings of multiple system atrophy (MSA), and dilatation of inferior horn of the lateral ventricle. In the next year, he lost of amburatory function, and showed low cognitive function of 5 scores in HDSR. At age 57, he was tracheostomised because of complete paralysis of the vocal cord abductor muscles. MRI study disclosed marked temporal lobe atrophy. He was complicated with bladder carcinoma, and died of multiple organ failure at age 66. The brain weight was 1,115 g. Gross neuropathological findings were temporal lobe dominant cerebral atrophy and marked pontocerebellar atrophy. Meningitis and sepsis were seen in the cerebrum, and some infarctions in the temporal and frontal lobes. Besides the typical degenerative findings of MSA, remarkable temporal lobe atrophy with enlargement of the inferior horn of lateral ventricle was observed. There were numerous number of neuron containing neuronal inclusion body (NCI) in the hippocampal cortex, dentate fascia and parahippocampal gyrus. In spite of small amount of NFT in the parahippocampal gyrus, there were no se- nile plaque, tau-positive structure except NFT, argyrophilic grain or Pick body. This case was a long-survived MSA with remarkable atrophy of the temporal lobe. The characteristic neuropathological finding was numerous numbers of neurons containing NCI in the cotices arround the inferior horn. Although frontal lobe dominant cerebral lobe atrophy is common in the long-survived MSA cases, extreme temporal lobe atrophy is rare condition. There may be a MSA subtype strongly affecting temporal lobe with numerous NCI.

Aged↗

PubMed2005

Neuropathologic characteristics of spinal cord lesions in sporadic Creutzfeldt-Jakob disease.

We investigated the neuropathologic features of spinal cord lesions in 23 patients with sporadic Creutzfeldt-Jakob disease (sCJD), paying particular attention to neuronal loss and gliosis, pyramidal tract degeneration and prion protein (PrP) deposition. The study included 9 cases of subacute spongiform encephalopathy, 13 cases of panencephalopathic-type sCJD and 1 case of sporadic fatal insomnia (sFI). In the spinal gray matter, although gliosis was present in some patients with disease of relatively long duration, the number of neurons, including large motor neurons, was well preserved regardless of disease duration. Pyramidal tract degeneration was observed in some patients with disease lasting more than 14 months but not in the patient with sFI. PrP deposition was present in the spinal cord of all sCJD patients, and was identified predominantly in the posterior horn, particularly in the substantia gelatinosa, regardless of disease duration or disease classification based on cerebral pathology. Relatively prominent PrP deposition was also observed in Clarke's column. The density of PrP deposition in the sCJD spinal cord was not associated with disease duration or neuronal degeneration. Our results indicate that PrP deposition in the spinal cord is an early pathologic event in sCJD and may remain to the end stage. Although no VV1, VV2 or MV2 cases were included in our study, we suggest that stereotypic accumulation of PrP is a consistent pathologic feature of sCJD and that the spinal cord remains relatively resistant to the pathologic process of sCJD, at least in patients with MM1 sCJD.

Adult↗

PubMed2005

Respiratory failure in a patient with antecedent poliomyelitis: amyotrophic lateral sclerosis or post-polio syndrome?

We report a 69-year-old man who developed paralytic poliomyelitis in childhood and then decades later suffered from fatal respiratory failure. Six months before this event, he had progressive weight loss and shortness of breath. He had severe muscular atrophy of the entire right leg as a sequela of the paralytic poliomyelitis. He showed mild weakness of the facial muscle and tongue, dysarthria, and severe muscle atrophy from the neck to proximal upper extremities and trunk, but no obvious pyramidal signs. Electromyogram revealed neurogenic changes in the right leg, and in the paraspinal, sternocleidomastoid, and lingual muscles. There was a slight increase in central motor conduction time from the motor cortex to the lumbar anterior horn. Pulmonary function showed restrictive ventilation dysfunction, which was the eventual cause of death. Some neuropathological features were suggestive of amyotrophic lateral sclerosis (ALS), namely Bunina bodies. In patients with a history of paralytic poliomyelitis who present after a long stable period with advanced fatal respiratory failure, one may consider not only respiratory impairment from post-polio syndrome but also the onset of ALS.

Aged↗

PubMed2005

An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains.

Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. By positional cloning, we have identified the gene strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed examination by use of audiogram suggested that sensorineural hearing impairment may be associated with ataxia in our families. After restricting the candidate region in chromosome 16q22.1 by haplotype analysis, we found that all patients from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide substitution, 16 nt upstream of the putative translation initiation site of the gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin-1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1 mRNA had an open reading frame of 3,576 nt, predicted to contain important domains, including the spectrin repeat and the guanine-nucleotide exchange factor (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi apparatus. Puratrophin-1--normally expressed in a wide range of cells, including epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also formed aggregates in Purkinje cells. The present study highlights the importance of the 5' untranslated region (UTR) in identification of genes of human disease, suggests that a single-nucleotide substitution in the 5' UTR could be associated with protein aggregation, and indicates that the GEF protein is associated with cerebellar degeneration in humans.

5' Untranslated Regions↗

PubMed2005

Neuropathologic characteristics of brainstem lesions in sporadic Creutzfeldt-Jakob disease.

We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pontine base, was relatively prominent in patients with disease of unusually prolonged duration. Neuronal loss and pyramidal tract degeneration were also identified in some but not all patients with prolonged disease. Neuronal loss was relatively prominent in the pontine nucleus and less so in the substantia nigra and inferior olivary nucleus; motor nuclei of the brainstem tegmentum were well preserved. PrP deposition was present in the brainstem in all patients, and was identified predominantly in the substantia nigra, quadrigeminal body, pontine nucleus, and inferior olivary nucleus. PrP deposition was less prominent in the red nucleus and tegmentum of the pons and medulla oblongata. PrP deposition occurred least or not at all in the pyramidal tract. The density of PrP deposition in the sCJD brainstem was not associated with disease duration or neuronal degeneration until the late stage. Our results show that atrophy, neuronal loss, and pyramidal tract degeneration occur in the sCJD brainstem, particularly in patients with an unusually prolonged disease course. These findings are not associated directly with PrP deposition and may reflect end-stage sCJD. No VV1, VV2, or MV2 cases were included in our study; however, we suggest that widespread and relatively stereotypic PrP deposition is a consistent pathologic feature of sCJD, at least in MM1 sCJD patients. Although accumulation of PrP in the brainstem appears to be an early pathologic event in sCJD, and may remain into the late disease stage, the brainstem remains relatively resistant to the pathologic process of sCJD.

Aged↗

PubMed2005

Widespread spinal cord involvement in corticobasal degeneration.

We examined spinal cord lesions in eight patients with a pathological diagnosis of corticobasal degeneration (CBD). Using Gallyas-Braak (G-B) staining or AT-8 tau immunostaining, a few neuropil threads were identified in the white matter of the CBD spinal cords, mainly in the anterior funiculus, whereas the posterior funiculus was well preserved without threads. In the gray matter of the CBD spinal cords, particularly in the intermediate gray matter, there were widespread neuropil threads and neuronal inclusions. Large motor neurons in the anterior horn, neurons in the intermediolateral column, and Clarke's column were relatively well preserved from neuronal loss and gliosis. Neuronal inclusions were of the globose type, suggestive of neurofibrillary tangles (NFTs), or showed diffuse granular accumulations of cytoplasmic tau, suggestive of pretangles. No typical NFTs, recognized by Bodian silver staining, were identified. The distribution of neuropil threads and G-B- or AT-8 tau-positive small neurons resembled that of interneurons. No astrocytic plaques were present in any of the CBD spinal cords, and only a few coiled bodies were seen. Neuropil threads in the white and gray matter and neuronal inclusions in the gray matter were prominent in cervical segments, and their density decreased caudally. We suggest that the presence of neuropil threads, particularly in the cervical intermediate gray matter, and the presence of neuronal inclusions, particularly in cervical interneurons, is an essential pathological feature of CBD.

Aged↗

PubMed2005

alpha-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy.

We immunohistochemically examined the sympathetic ganglia (SG) and brains of 26 patients with multiple system atrophy (MSA), 19 age-matched controls, and 25 patients with amyotrophic lateral sclerosis (ALS). alpha-Synuclein-immunoreactive structures were found in the neuronal cytoplasm and processes of the SG in 11 of the 26 MSA cases (42.3%) and 1 of the 25 ALS cases (4%), but not in the 19 controls. No alpha-synuclein-immunoreactive structures were found in Schwann cells or the neuronal nucleus. Mean disease duration of MSA cases with alpha-synuclein-immunoreactive structures was significantly longer than that of MSA cases without alpha-synuclein-immunoreactive structures. alpha-Synuclein-immunoreactive structures in 4 cases proved to be Lewy bodies (LB) based on hematoxylin-eosin staining. A few LB were also found in the brains of 3 of these 4 cases. In the other 7 MSA cases, diffuse or focal neuronal cytoplasmic aggregates and swollen neurites were detected with alpha-synuclein immunostaining, but not with hematoxylin-eosin staining. However, a few LB-like structures with ring-like staining were observed in those aggregates, which suggested those aggregates had progressed to form LB. Immunoelectron microscopically, those aggregates were composed of filaments and granular materials which closely resembled the ultrastructural features of LB. We inferred that alpha-synuclein aggregates found in the SG in our study evidenced LB-related pathologies. MSA, a type of synucleinopathy, is characterized by glial cytoplasmic inclusions in oligodendrocytes, but also frequently develops LB pathology in the late stage, especially in the SG.

Aged↗

PubMed2005

Tuft-shaped astrocytes in Lewy body disease.

We investigated the occurrence and distribution of tuft-shaped astrocytes (TuSAs) in 60 brains from patients with Lewy body disease (LBD), which were clinically diagnosed as Parkinson's disease (PD) or dementia with Lewy bodies (DLB), and 85 brains from control subjects. TuSAs have been documented as a neuropathological hallmark of progressive supranuclear palsy (PSP). We found phosphorylated tau (p-tau)-positive and alpha-synuclein-negative TuSAs in 10 of 60 patients with LBD and 3 of 85 control cases. TuSAs were mainly located within the precentral and premotor gyri of the frontal lobe cortex. There were only few TuSAs, but the distribution pattern and morphological and immunohistological features were similar to that in PSP. Furthermore, other p-tau positive structures, including aggregates in neurons, coiled-like glial cells and threads showed a similar distribution to those in PSP; mainly in the hippocampus, striatum, subthalamic nucleus, precentral and premotor gyri, brainstem nucleus, and dentate nucleus. In these cases, however, neuronal loss and gliosis were not seen in the regions involved in PSP, such as the subthalamic nucleus, pallidum, inferior olivary, cerebellar dentate nuclei, and periaqueductal gray matter. Clinical features were indistinguishable between the LBD with and without TuSAs. The appearance of TuSAs was not related to the frequency of Lewy bodies, neurofibrillary tangles, and senile plaques, but was significantly more pronounced with advancing age in both LBD and controls. These findings suggest that in a subgroup of elderly individual cases, especially associated with LB pathology, the glial and neuronal p-tau accumulation is increased and has a distributional pattern similar to PSP.

Aged↗

PubMed2005

Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients.

Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The characteristic pathological finding is nuclear inclusions (NIs) consisting of mutant AR with an expanded polyQ in residual motor neurons, and in certain visceral organs. We immunohistochemically examined 11 SBMA patients at autopsy with 1C2, an antibody that specifically recognizes expanded polyQ. Our study demonstrated that diffuse nuclear accumulation of mutant AR was far more frequent and extensive than NIs being distributed in a wide array of CNS nuclei, and in more visceral organs than thus far believed. Mutant AR accumulation was also present in the cytoplasm, particularly in the Golgi apparatus; nuclear or cytoplasmic predominance of accumulation was tissue specific. Furthermore, the extent of diffuse nuclear accumulation of mutant AR in motor and sensory neurons of the spinal cord was closely related to CAG repeat length. Thus, diffuse nuclear accumulation of mutant AR apparently is a cardinal pathogenetic process underlying neurological manifestations, as in SBMA transgenic mice, while cytoplasmic accumulation may also contribute to SBMA pathophysiology.

Aged↗