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Kenji Kosaka

Publications and source records attributed to Kenji Kosaka.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Clinical aspects of dementing illnesses in the elderly].

Clinical aspects of dementing illnesses in the elderly were briefly reviewed. Symptomatic classification of dementia by Harada and clinicopathological classification by Kosaka were first introduced. After that, three major dementing illnesses: 1) Alzheimer's disease, 2) dementia with Lewy bodies and 3) vascular dementia were briefly explained, focusing on clinical aspects. In addition, limbic neurofibrillary tangle dementia (LNTD) was also introduced, the frequency of which is expected to increase in the future because of increasing number of the "old old" elderly.

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PubMed2004

Promoter polymorphism in fibroblast growth factor 1 gene increases risk of definite Alzheimer's disease.

Fibroblast growth factor 1 (FGF1, also known as acidic FGF) protects selective neuronal populations against neurotoxic effects such as those in Alzheimer's disease (AD) and HIV encephalitis. The FGF1 gene is therefore a strong candidate gene for AD. Using the promoter polymorphism of the FGF1 gene, we examined the relationship between AD and the FGF1 and apolipoprotein E (APOE) genes in 100 Japanese autopsy-confirmed late-onset AD patients and 106 age-matched non-demented controls. The promoter polymorphism (-1385 A/G) was significantly associated with AD risk. The odds ratio for AD associated with the GG vs non-GG genotype was 2.02 (95% CI = 1.16-3.52), while that of s4 vs non-ł4 in APOE4 gene was 5.19 (95% CI = 2.68-10.1). The odds ratio for APOEP4 and FGF1 GG carriers was 20.5 (95% CI = 6.88-60.9). The results showed that the FGF1 gene is associated with autopsy-confirmed AD.

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PubMed2004

Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease.

We reclassified the pathological subtypes of dementia with Lewy bodies (DLB), based on both Lewy pathology and Alzheimer pathology, to clarify the pathological entity of DLB and the boundary between DLB and Alzheimer's disease (AD) in autopsied cases, using both pathological and immunohistochemical methods. DLB was classified as either limbic type or neocortical type according to the degree of Lewy pathology including Lewy bodies (LB) and LB-related neurites by our staging, and was classified as pure form, common form or AD form according to the degree of Alzheimer pathology including neurofibrillary tangles (NFT) and amyloid deposits by Braak staging. These combined subtypes were lined up on a spectrum, not only with Lewy pathology but also with other DLB-related pathologies including Alzheimer pathology, neuronal loss in the substantia nigra, spongiform change in the transentorhinal cortex and LB-related neurites in the CA2-3 region. In contrast, the Lewy pathology of AD did not meet the stages of Lewy pathology in DLB, and there were scarcely any similarities in other DLB-related pathologies between AD and DLB. In addition, the Lewy pathology of AD had characteristics different from that of DLB, including the coexistence rate of LB with NFT, and the immunohistochemical and immunoelectron microscopic findings of LB and LB-related neurites. These findings suggest that DLB is a distinctive pathological entity that can be differentiated from AD, although it shows some pathological subtypes.

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PubMed2004

Immunohistochemical study of tau accumulation in early stages of Alzheimer-type neurofibrillary lesions.

Accumulation of abnormally phosphorylated tau results in the formation of neurofibrillary tangles (NFTs) in the neuronal cell soma and neuropil threads (NTs) in the cell processes. In the present study, we used immunohistochemistry to investigate serially cut thick tissue sections from the brains of patients with Alzheimer's disease (AD) and non-demented elderly subjects. In the early stages of neurofibrillary pathology, clusters of NTs occurred occasionally in the cerebral cortex. Each NTs cluster, the entire extent of which was observed in the serial sections, corresponded to a dendritic tree that was arborized from a tau-positive neuron. Adult human brain contains six tau isoforms with three having three carboxyl-terminal tandem repeat sequences that are encoded by exon 10 (3R-tau) and the other three having four repeat sequences (4R-tau). Three isoform patterns, 3R-tau(+)/4R-tau(-), 3R-tau(-)/4R-tau(+) and 3R-tau(+)/4R-tau(+), were seen in NFTs in early stage AD lesions. In an individual neuron, the isoform pattern was consistent between the NFTs in the cell soma and the NTs in the cell processes. The results of this study indicate that, in early stages of AD and age-associated neurofibrillary changes, tau accumulates simultaneously in the cell soma and cell processes of affected neurons. The process of AD and age-associated tau pathology is not tau-isoform-specific, but the ratio of 3R-tau and 4R-tau isoforms involved in the neurofibrillary changes varies and is specific to individual neurons.

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PubMed2004

Activation of vascular endothelial cells and perivascular cells by systemic inflammation-an immunohistochemical study of postmortem human brain tissues.

We investigated postmortem human brain tissues to determine whether systemic inflammation causes activation of vascular endothelial cells and perivascular cells. In some cases, we used serum concentrations of an acute-phase reactant, C-reactive protein (CRP), as an index of systemic inflammation. Since the serum concentration of CRP at the agonal stage was available only in a limited number of patients, we estimated the degree of systemic inflammation by the intensity of immunohistochemical staining of the residual blood in brain tissue for CRP. Expressions of intercellular adhesion molecule (ICAM)-1, CD40 and cyclooxygenase (COX)-2 were used as markers for activation of vascular endothelial cells. Activation of perivascular cells was estimated by the occurrence of HLA-DR- and CD68-positive perivascular cells. In cases without brain lesions, activation of vascular endothelial cells and perivascular cells was related to the degree of systemic inflammation. In cases with brain lesions, these cells are often activated even in the absence of systemic inflammation. We suggest that inflammatory stimuli derived from the peripheral blood and the brain parenchyma adjunctly activate vascular cells. Under such circumstances, low-grade inflammation in the pre-existing brain lesions might enhance inflammatory signaling to the brain parenchyma from the periphery. The results of this study could explain the vulnerability of neurological patients to delirium caused by systemic inflammatory conditions.

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PubMed2004

Serum adiponectin concentrations during treatment with olanzapine or risperidone: a pilot study.

Adiponectin is a recently identified adipocyte-derived protein, which is associated with glucose metabolism, insulin sensitivity and adiposity. The aim of this study was to explore the alterations in serum adiponectin concentration during treatment with olanzapine or risperidone. Serum concentrations of adiponectin were investigated in body mass index (BMI, kg/m2)- and age-matched groups of non-diabetic, non-obese schizophrenic patients receiving a stable dose of olanzapine (n = 18) or risperidone (n = 15) for 4 weeks or more, and of mentally and physically healthy volunteers (n = 17). Patients undergoing treatment with olanzapine or risperidone had significantly higher adiponectin concentrations than the healthy volunteers, even after controlling for BMI. Adiponectin concentrations decreased with increasing BMI in patients taking olanzapine, while elevated levels were observed in patients taking risperidone, regardless of adiposity. This preliminary cross-sectional study indicates that adiponectin is involved in the regulation of glucose metabolism and weight in schizophrenic patients during treatment with olanzapine or risperidone, presumably showing a normalizing effect on metabolic abnormality.

Adiponectin↗
PubMed2004

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction.

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.

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PubMed2004

Ubiquitin and ubiquitin-related proteins in neurons and dendrites of brains of atypical Pick's disease without Pick bodies.

Nine cases of atypical Pick's disease without Pick bodies were investigated immunohistochemically. Ubiquitin (ub)-positive and tau-negative structures were mainly found in the cerebral cortex and hippocampal dentate gyrus. In the cerebral cortex, most of the ub-positive structures had ub-positive dendrites in the neuropil, although some also showed diffuse ub-positive staining in the neuronal cytoplasm. These ub-positive structures were distributed throughout layers II-IIIab and layers V-VI. Granular cells of the dentate gyrus had ub-positive intraneuronal inclusions. When the numbers of ub-positive neurons and dendrites were evaluated in relation to the degree of neuronal loss in the cerebral cortex, the number of ub-positive neurons was significantly lower in regions showing very mild neuronal loss and higher in regions showing moderate neuronal loss. In contrast, ub-positive dendrites were detected even in cortical regions showing very mild neuronal loss. Immunoelectron-microscopically, ub-positive structures contained ub-positive ribosome-like granular components in the neuronal cytoplasm and dendrites, which were occasionally related to the rough endoplasmic reticulum and accompanied by a few filamentous components. Almost all ub-positive structures were positive for ub-binding protein p62 in double-immunostaining method. Some ub-positive or negative neurons in the cerebral cortex were positively immunolabeled with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase antibodies, whereas dendrites were not labeled by these antibodies. From the present study, it is suggested that in the cerebral cortex, these ubiquitinated proteins may firstly accumulate in the dendrites at the onset of neuronal degeneration, then appear in the neuronal cytoplasm before finally disappearing with neuronal loss.

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PubMed2004

Ubiquitin and ubiquitin-related proteins in the brains of patients with atypical Pick's disease without Pick bodies and dementia with motor neuron disease.

Nine cases of atypical Pick's disease without Pick bodies (aPiD) and seven cases of dementia with motor neuron diseases (D-MND) were compared using immunohistochemistry of ubiquitin (ub) and ub-related proteins. All cases showed rostral-dominant atrophy in the temporal and frontal lobes, although the degree of atrophy with neuronal loss was much more severe in the aPiD cases. In both aPiD and D-MND cases, ub-positive and tau-negative structures were found mainly in the hippocampal dentate gyrus and cerebral cortex. Granular cells of the dentate gyrus showed similar ub-positive intraneuronal inclusions in both cases. In the aPiD cases, most of the ub-positive cortical structures were ub-positive dendrites in layers II-IIIab and layers V-VI, although some neurons also showed diffuse ub-positive staining in the cytoplasm. In the D-MND cases, some neurons showed ub-positive inclusions in layers II-IIIab, and ub-positive dendrites were unremarkable. The number of ub-positive neurons and dendrites in relation to the degree of neuronal loss in the cerebral cortex were then evaluated. The number of ub-positive neurons in the regions showing very mild to mild neuronal loss was significantly greater in the D-MND cases than in the aPiD cases. However, in the aPiD cases, the number of ub-positive neurons was significantly greater in the regions showing moderate neuronal loss. When double-immunostained, almost all ub-positive structures were positive for ub-binding protein p62. Some ub-positive or negative neurons in the cerebral cortex were immunostained with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase (UCH-L1) antibodies. Granular cells of the dentate gyrus were weakly positive for UCH-L1. There could be some differences in the mechanism by which neurons in the cerebral cortex accumulate ub between aPiD and D-MND.

Adult↗
PubMed2004

Psychomotor retardation correlates with frontal hypoperfusion and the Modified Stroop Test in patients under 60-years-old with major depression.

Frontal hypoperfusion and frontal dysfunction have been reported in patients with major depression. It was also found that frontal hypoperfusion correlated with frontal dysfunction evaluated by neuropsychological tests in depressive patients aged 60 or over. These findings suggested that depression may cause frontal dysfunction and frontal hypoperfusion, and that these pathophysiological changes are manifested as psychomotor retardation. We performed single photon emission computed tomography and Modified Stroop Test on 35 patients with depression aged 25-83 to investigate association of depressive symptoms and psychological tests with cerebral blood perfusion. Additionally, we divided the patients into a younger (less than 60 years old) and an older (60 or over) group to examine the effect of age. Significant correlations were found between frontal perfusion, interference measure on Modified Stroop Test, and psychomotor retardation in all patients. These correlations were also found in the younger group. There was no significant difference on frontal perfusion, interference measure of the Modified Stroop Test, and psychomotor retardation between the two groups. The present findings suggest that frontal hypoperfusion, frontal dysfunction, and psychomotor retardation were associated with one another in not only the old but also the young patients with depression.

Adult↗
PubMed2004

The splicing regulatory protein p18SRP is down-regulated in Alzheimer's disease brain.

Alzheimer's disease (AD) is the most common neurodegenerative disorder of aging, accounting for an estimated two-thirds of all cases of senile dementia. Using bioinformatics, the yeast two-hybrid-system, reverse transcription polymerase chain reaction, and fluorescence microscopy analysis, we demonstrate here that the new putative splicing regulatory protein p18SRP is a lysine-rich zinc finger domain-containing protein that interacts with the serine-arginine (SR)-rich splicing regulatory protein SRrp86. The additional finding of its down-regulation in the brain of AD subjects points to a possible pivotal role of p18SRP in the control of cellular survival.

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PubMed2004

[A case with late-onset MELAS with hallucination and delusion].

We report a 53-year-old male patient with late onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes(MELAS) with hallucination and delusion. The patient manifested various neurological symptoms including perceptive deafness, muscle weakness of limbs with loss of consciousness, sensory abnormalities in hands, feet and a face, abnormal sense of taste, tremor, palsy of upward eye movement and weak deep tendon reflexes prior to the psychotic episode. He was diagnosed as MELAS, because of high serum lactic acid and pyruvic acid, and the point mutation in the mitochondrial DNA 3243. SPECT imaging showed decreased perfusion in occipital cortex and thalamus. These SPECT changes improved after disappearing visual hallucination. Hallucination might be caused by delirium due to stroke-like episode. Dysfunction in the occipital cortex and thalamus might be involved with this perfusion change.

Delusions↗
PubMed2003

Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson's disease with dementia.

The relationship between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) has been insufficiently described, and it is still problematic. Twenty-nine cases of DLB and 10 cases of PDD were investigated in the present study. DLB cases disclosed a significantly older disease onset and shorter disease duration than PDD cases (p<0.01 each). However, they showed no significant difference in dementia onset or dementia duration (p>0.05 each). Motor symptoms (parkinsonism) were suspected as the cause of the younger disease onset in PDD cases. Compared with 10 age-matched cases of definite Alzheimer's disease, both 19 DLB cases and 6 PDD cases had significantly better scores in the final test of mini-mental state examination (MMSE) and revised version of Hasegawa's Dementia Scale (HDSR) within 12 months before death, although no significant differences between DLB and PDD were indicated. DLB and PDD were suspected to show cognitive impairment of similar severity in the terminal stage. They would thus be difficult to classify as completely different entities.

Age of Onset↗
PubMed2003

Serum ghrelin concentrations in patients receiving olanzapine or risperidone.

RATIONALE: Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanism is poorly understood. OBJECTIVES: To test the hypothesis that ghrelin, a gastrointestinal hormone that enhances appetite, is involved in increased food intake and weight gain during treatment with antipsychotics. METHODS: Serum ghrelin concentrations were investigated in schizophrenic patients receiving olanzapine or risperidone, and in healthy volunteers. RESULTS: Serum ghrelin concentrations did not increase, but rather decreased, in patients treated with olanzapine or risperidone in comparison with healthy volunteers. No significant difference was found in serum ghrelin concentration between patients treated with olanzapine and risperidone. CONCLUSIONS: Our results indicate that ghrelin is not a direct cause of increased food intake and weight gain during treatment with olanzapine or risperidone, whereas ghrelin is associated with metabolic change in patients receiving these agents.

Adult↗
PubMed2003

Developmental stages of cortical Lewy bodies and their relation to axonal transport blockage in brains of patients with dementia with Lewy bodies.

We investigated 10 dementia with Lewy bodies (DLB) brains showing various degrees of Lewy pathology using alpha-synuclein-immunohistochemistry, and morphologically divided cortical Lewy bodies (LB) into six developmental stages. Further, we demonstrated the ultrastructure of each stage of cortical LB using alpha-synuclein-immunoelectron microscopy. In the initial stage, alpha-synuclein accumulated in part of the neuronal cytoplasm without filamentous components, then formed LB and LB-related neurites composed of granulo-filamentous components. Finally, LB degraded to extracellular LB composed of loose filamentous components with involved astroglial processes. In addition, we immunohistochemically investigated the accumulation of axonal transported substances in cortical LB, and showed that APP, chromogranin-A, synphilin-1 and synaptophysin accumulated in cortical LB from stages 1, 2, 3 and 4, respectively. These findings suggest that chronic axonal transport blockage is implicated in the development of cortical LB in DLB brains.

Amyloid beta-Protein Precursor↗
PubMed2003

4-repeat tauopathy sharing pathological and biochemical features of corticobasal degeneration and progressive supranuclear palsy.

We report a 67-year-old man with 4-repeat (4R) tauopathy sharing both features of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Although CBD and PSP have a common pathological feature that 4R tau accumulates in neurons and glia, recent pathological studies have confirmed differences between the two disorders. Clinical features of the present case were asymmetrical apraxia, parkinsonism, memory disturbance, disorientation and left limb myoclonus with a 5-year history. Pathological features were the widespread occurrence of 4R tau-positive structures including pre-tangles, neurofibrillary tangles, astrocytic plaques, tufted astrocytes, coiled bodies and argyrophilic threads. Biochemically, immunoblotting of insoluble tau demonstrated the low molecular fragments of 37 kDa and 33 kDa observed in typical CBD and PSP, respectively, in addition to the presence of 4R tau isoforms. The present case shared tau-related pathological and biochemical features of CBD and PSP. These findings support that CBD and PSP are closely associated disorders having a pathogenesis common to 4R tauopathy.

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