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Eizo Iseki

Publications and source records attributed to Eizo Iseki.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical investigation of neurofibrillary tangles and their tau isoforms in brains of limbic neurofibrillary tangle dementia.

Limbic neurofibrillary tangle dementia (LNTD) is a subset of senile dementia characterized by numerous neurofibrillary tangles (NFT) in the hippocampal area, although there is an absence or scarcity of amyloid deposits (AM) throughout the brain. In the present study, we immunohistochemically investigated regional numbers and tau isoforms of NFT in the hippocampal area of nine LNTD patients with anti-three-repeat (3R) tau-specific and anti-four-repeat (4R) tau-specific antibodies, differentiating NFT into three developmental stages of pretangles (PT), NFT and ghost tangles (GT). Consequently, most PT were 4R tau-positive, most GT were 3R tau-positive, and NFT were 3R tau-, 4R tau- or double-positive, suggesting that composition of tau isoforms may shift from a 4R tau-predominant pattern to a 3R tau-predominant pattern during the development of NFT. In addition, a large number of NFT showing different developmental stages and different rates of 3R tau- and 4R tau-positive neurons according to the region were found in the hippocampal area, suggesting that regions undergoing earlier NFT formation may show higher ratio of 3R tau-positive neurons to 4R tau-positive neurons, and that NFT formation may begin in the entorhinal and transentorhinal cortices, subsequently progress to the subiculum and CA1, and further to the CA2, amygdala and CA3-4, although progression to the neocortex is limited. Furthermore, 4R tau-positive astrocytes and grains were found in several patients, suggesting that LNTD is a form of tauopathy.

Aged, 80 and over↗
PubMed2006

Relative paucity of tau accumulation in the small areas with abundant Abeta42-positive capillary amyloid angiopathy within a given cortical region in the brain of patients with Alzheimer pathology.

Cerebral amyloid angiopathy (CAA) is a manifestation of amyloid beta-protein (Abeta) accumulation in the elderly as well as in patients with Alzheimer's disease (AD). Two types of CAA have been noted, based on the type of vasculature in which Abeta is deposited: cerebral capillary amyloid angiopathy (capCAA) and non-capCAA. Non-capCAA is a common form of CAA that consists of Abeta deposited in arteries and arterioles. Recent information on Abeta metabolism in the brain suggests that non-capCAA is associated with Abeta secretion into the cerebrospinal fluid via the perivascular space, whereas capCAA is associated with Abeta removal to blood plasma via the capillary endothelium. Abeta40, a major and relatively soluble Abeta isoform, is deposited predominantly in non-capCAA, and Abeta42, which is insoluble and associated more closely than Abeta40 with AD, is deposited predominantly in capCAA. Studying small areas of microscopic size within a given cortical region, we found an inverse association of capCAA and senile plaques. We also found a relative paucity of tau pathology in the small areas with abundant capCAA compared with the small areas with abundant senile plaques within a cortical region with the same cytoarchitecture. We suppose that both capCAA and senile plaques indicate high Abeta42 in the neuropil but that only Abeta42 in the form of insoluble deposits in senile plaques promotes tau abnormality.

Aged↗
PubMed2006

Investigation of Lewy pathology in the visual pathway of brains of dementia with Lewy bodies.

We examined 19 autopsied cases of dementia with Lewy bodies (DLB) using pathological and alpha-synuclein-immunohistochemical methods, and investigated Lewy pathology in the primary visual pathway (lateral geniculate body and Brodmann's area 17), secondary visual pathway (pulvinar, Brodmann's areas 18 and 19, and inferior temporal cortex), amygdala and substantia nigra, to clarify the relationship between visual misidentification and Lewy pathology in the visual pathway. Consequently, the secondary visual pathway revealed significantly severer Lewy pathology than the primary visual pathway, suggesting that the degeneration of the secondary visual pathway induces dysfunction in the recognition of objects shape and color. In addition, the amygdala revealed significantly severer Lewy pathology and neuronal loss than the primary and secondary visual pathways, suggesting that the degeneration of the amygdala, which receives the afferent connections from the substantia nigra, fails to modulate the visual processing according to cognition and emotion. These findings suggest that Lewy pathologies in the secondary visual pathway and amygdala may cause the dysfunction of the visuo-amygdaloid pathway and participate in visual misidentification in DLB patients. In addition, we compared Lewy pathology between cases with and without visual hallucinations, and showed no significant differences between the two groups.

Aged↗
PubMed2006

An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies.

The pathological distinctions between the various clinical and pathological manifestations of frontotemporal lobar degeneration (FTLD) remain unclear. Using monoclonal antibodies specific for 3- and 4-repeat isoforms of the microtubule associated protein, tau (3R- and 4R-tau), we have performed an immunohistochemical study of the tau pathology present in 14 cases of sporadic forms of FTLD, 12 cases with Pick bodies and two cases without and in 27 cases of familial FTLD associated with 12 different mutations in the tau gene (MAPT), five cases with Pick bodies and 22 cases without. In all 12 cases of sporadic FTLD where Pick bodies were present, these contained only 3R-tau isoforms. Clinically, ten of these cases had frontotemporal dementia and two had progressive apraxia. Only 3R-tau isoforms were present in Pick bodies in those patients with familial FTLD associated with L266V, Q336R, E342V, K369I or G389R MAPT mutations. Patients with familial FTLD associated with exon 10 N279K, N296H or +16 splice site mutations showed tau pathology characterised by neuronal neurofibrillary tangles (NFT) and glial cell tangles that contained only 4R-tau isoforms, as did the NFT in P301L MAPT mutation. With the R406W mutation, NFT contained both 3R- and 4R-tau isoforms. We also observed two patients with sporadic FTLD, but without Pick bodies, in whom the tau pathology comprised only of 4R-tau isoforms. We have therefore shown by immunohistochemistry that different specific tau isoform compositions underlie the various kinds of tau pathology present in sporadic and familial FTLD. The use of such tau isoform specific antibodies may refine pathological criteria underpinning FTLD.

Adult↗
PubMed2006

Efficacy and safety of donepezil in patients with dementia with Lewy bodies: preliminary findings from an open-label study.

The objectives of the present study were first to determine the feasibility of conducting a randomized clinical trial of 5 mg/day donepezil in patients with mild to moderate dementia with Lewy bodies (DLB) and second, to obtain preliminary data of possible intervention effects. Twelve patients with probable DLB were evaluated at weeks 4, 8, and 12 using modified Neuropsychiatric Inventory (NPI) with an extra domain to additionally evaluate fluctuation in cognitive functions (NPI-11); the Japanese version of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog); and the Unified Parkinson's Disease Rating Scale (UPDRS). The NPI-11 scores were significantly improved at weeks 8 and 12 compared with baseline. Despite a significant improvement in ADAS-J-cog at week 4, no more improvement was noted thereafter. Deterioration was not noted in UPDRS scores. Donepezil is expected to be therapeutically useful and safe in treating DLB patients, indicating marked improvements in behavioral and psychological symptoms of dementia (BPSD) rather than in cognitive deficit, without deteriorating parkinsonism.

Aged↗
PubMed2005

The nigro-striatal and nigro-amygdaloid pathways undergo different degeneration processes in brains of dementia with Lewy bodies.

We immunohistochemically investigated the degeneration processes of the nigro-striatal and nigro-amygdaloid pathways and the relationship between the loss of dopaminergic neurons and Lewy bodies (LB) formation in the substantia nigra using 15 autopsied cases of dementia with Lewy bodies (DLB). The number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and TH-positive axonal terminals in the putamen decreased with a specific pattern. The substantia nigra possessed alpha-synuclein-positive LB-bearing neurons that were almost evenly distributed, while the putamen exhibited diffuse or granular alpha-synuclein-immunostaining. Most of the granular stains were positive for anti-phosphorylated alpha-synuclein antibody, whereas the diffuse stains were negative. These findings suggest that the axonal terminals in the putamen undergo abnormal alpha-synuclein accumulation, but may not always originate from LB-bearing neurons in the substantia nigra. The central amygdaloid nucleus contained anti-alpha-synuclein- and -phosphorylated alpha-synuclein-positive dystrophic axonal terminals, the degree of which was greater for cases with granular staining in the putamen, and which was proportional to the number of alpha-synuclein-positive neurons in the substantia nigra. Thus, the axonal terminals in the central amygdaloid nucleus may have originated from LB-bearing neurons in the substantia nigra. The results of the present study indicate that the nigro-striatal and nigro-amygdaloid pathways undergo different degeneration processes in DLB, and suggest that the degeneration of the nigro-amygdaloid pathway more strongly reflects LB formation in dopaminergic neurons of the substantia nigra than that of the nigro-striatal pathway. In addition, they indicate that there is no direct relationship between the loss of dopaminergic neurons and LB formation in the substantia nigra.

Aged↗
PubMed2005

Non-uniformity in the regional pattern of Lewy pathology in brains of dementia with Lewy bodies.

We examined the regional pattern of Lewy pathology in brains of dementia with Lewy bodies (DLB) to clarify whether Lewy pathology uniformly progresses or not. Thirty-five autopsied DLB cases were examined using alpha-synuclein-immunohistochemistry, and the regional degree of Lewy pathology in the brainstem, diencephalon and cerebral cortex was quantitatively evaluated. Consequently, we found that the regional pattern of Lewy pathology differed according to the pathological subtype, and was divided into three types: type 1 showed a brainstem-predominant pattern, type 2 was almost equal for the brainstem and cerebral cortex, and type 3 showed a cerebral cortex-predominant pattern. The limbic type/pure and common forms were mainly composed of type 1, whereas the neocortical type/common and Alzheimer's disease (AD) forms were mainly composed of type 3. These findings suggest the possibility that Lewy pathology of the limbic type/pure and common forms mainly progresses from the brainstem to the cerebrum, whereas that of the neocortical type/common and AD forms mainly progresses from the cerebrum to the brainstem. Cases with type 1 Lewy pathology mainly developed parkinsonism, whereas those with type 3 Lewy pathology mainly developed dementia. This corresponded to most of the limbic type/ pure and common forms which developed parkinsonism, whereas most of the neocortical type/common and AD forms developed dementia. Type 1 cases may thus be clinically diagnosed as having Parkinson's disease (PD) with dementia. These findings suggest that PD has clinico-pathological continuity with DLB, and that the regional pattern of Lewy pathology is not uniform.

Aged↗
PubMed2005

Self-burning versus self-cutting: patterns and implications of self-mutilation; a preliminary study of differences between self-cutting and self-burning in a Japanese juvenile detention center.

The purpose of the present paper was to examine the differences in clinical features between self-cutters and self-burners, to clarify clinical implications of self-mutilating behaviors other than self-cutting. Subjects were 201 delinquent adolescents consecutively entering a Japanese juvenile detention center from February 2003 to March 2003. The subjects were assessed using a self-reporting questionnaire to evaluate self-mutilation, traumatic events, and problematic behaviors. Beck Depression Inventory-2 (BDI-2) and Adolescent Dissociative Experience Scale (A-DES) were also tested. Subjects were classified into four groups according to self-mutilating behaviors: non-self-cutting or -burning (NSCB), self-cutting (SC), self-burning (SB), and self-cutting and self-burning (SCB). The questionnaire answers and scores of the BDI-2 and A-DES were compared between the four groups. Of 201 subjects, 33 (16.4%) had cut their wrists or forearms at least once, and 72 of 201 (35.8%) had burned themselves at least once. The SC and SCB group had traumatic events, problematic behavior, and various types of self-mutilating behavior more frequently than the other two groups. The SCB group reported additional types of self-mutilating behavior more than the SC group. The SCB group also experienced multiple body customizations compared to the SC group, and exhibited higher scores on the BDI-2 and A-DES than the other three groups. The self-burning without self-cutting may have limited clinical implications. However, the self-burning with self-cutting may suggest depression and dissociation, as well as possible indication of self-mutilating behavior.

Adolescent↗
PubMed2005

Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report.

The present study examined childhood histories of attention-deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P=0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P=0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut-off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.

Adolescent↗
PubMed2005

Drug preferences in illicit drug abusers with a childhood tendency of attention deficit/hyperactivity disorder: a study using the Wender Utah Rating Scale in a Japanese prison.

The purpose of this study is to clarify the relationship between childhood tendencies of attention deficit/hyperactivity disorder (AD/HD) and illicit drug abuse in Japanese prisoners, and to clarify whether drug abusers with AD/HD prefer methamphetamine (MAP) more than other illicit drugs. The Japanese version of the Wender Utah Rating Scale (WURS), which is a self-reporting instrument to retrospectively identify childhood tendencies of AD/HD tendencies, was carried given to 413 prisoners without a drug addiction and 282 prisoners with a drug addiction (192, MAP; 53, toluene; and 37, cannabis). WURS scores were compared between prisoners with and without a drug addiction, and between MAP, toluene, and cannabis abusers. Consequently, prisoners with a drug addiction showed significantly higher WURS scores than those without the addiction (P < 0.001). Toluene abusers showed significantly higher WURS scores than cannabis abusers (P < 0.001), and included a higher proportion with scores over cut-off than MAP or cannabis abusers (P = 0.005). In conclusion, a close relationship existed between illicit drug abuse and childhood AD/HD tendencies. Drug-abusing prisoners with AD/HD tendencies were not prone to choose MAP over other illicit drugs.

Adolescent↗
PubMed2005

Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms.

OBJECTIVE: Although argyrophilic grain disease (AGD) appears common in post-mortem series, its clinical features are not widely known. The aim of this study was to explore such clinical features in neuropathologically-confirmed AGD cases. METHODS: After completing a neuropathological assessment of 386 patients, 33 cases (8.5%) were diagnosed as having AGD; 10 were diagnosed as "pure" cases. These subjects had been admitted to geriatric wards of mental hospitals because of behavioral or neuropsychiatric symptoms requiring medical management. Assessment of the clinical features of the pure cases was based on the evaluations in medical records. RESULTS: The average age at onset was 82.2 years. Amnesia was the most common initial symptom; irritability and agitation were also common as initial symptoms. During the course of the illness, irritability was the most frequently observed, followed by delusions (mostly delusions of persecution), dysphoria, and then agitation, and apathy. In contrast to the severity of amnesia, other cognitive functions were relatively spared, and the sensorimotor symptoms were not remarkable. CONCLUSIONS: AGD is a late-onset dementing disorder clinically characterized by amnesia, with other cognitive functions relatively spared, and prominent neuropsychiatric features. These features may correlate with the high level of AGD seen in limbic structures. Future studies are needed to elucidate whether these features are common to all AGD patients or to a clinical subtype with neuropsychiatric symptoms.

Aged↗
PubMed2005

[Dementia with Lewy bodies].

"Dementia with Lewy bodies (DLB)" was proposed at the first international workshop in 1995. It has received much attention since we had proposed "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. In the CDLB guidelines, which were reported in 1996, the clinical and pathological diagnostic criteria for DLB were shown for the first time. At present, DLB as well as Alzheimer's disease (AD) and vascular dementia (VD) are known as the three major dementing illnesses. The second international workshop was held in 1998, and the third in 2003. One of the authors, K. Kosaka, presented a paper on DLB at each international workshop, based on series of our papers which we had reported since 1976. The revised CDLB guidelines will be reported soon. In addition, the fourth international workshop on DLB will be held by Kosaka in Yokohama in 2007. In this article, we review the history, the clinical, therapeutic, neuropathological, neurochemical and molecular biological issues, based on our previous papers and other important reports on DLB.

Acetylcholine↗
PubMed2004

Decrease in GTP-sensitive high affinity agonist binding of muscarinic acetylcholine receptors in autopsied brains of dementia with Lewy bodies and Alzheimer's disease.

To determine changes in signal transduction from the muscarinic acetylcholine receptor (mAChR) to G protein in brain tissue of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we investigated GTP-sensitive agonist high affinity binding, which is considered an index of the formation of the mAChR-G protein complex. Brain tissue was obtained at necropsy from eight patients with DLB, nine patients with Alzheimer's disease and seven patients as controls. Membrane fractions were prepared from frontal and temporal cerebral tissues. Displacement curves of [(3)H]l-quinuclidinyl benzilate (QNB) binding by carbamylcholine were analyzed by the nonlinear least-squares methods. The proportion of and affinity for the agonist in GTP-sensitive agonist high affinity binding were estimated. The percentages GTP-sensitive agonist high affinity bindings were significantly decreased in DLB (P<0.01) and Alzheimer's disease (P<0.05) only in the frontal lobe. There were no significant differences in the temporal lobe. The ratio of agonist affinity (Kd value of low affinity component/Kd value of high affinity component) did not significantly differ among groups in either the frontal lobe or temporal lobe. The concentration of mAChR-G protein complex is considered reduced in the frontal lobe of brains with DLB and Alzheimer's disease. Therefore, signal transduction from mAChR to G protein was disturbed in the frontal lobe in these diseases.

Aged↗
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.

Aged↗
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.

Aged↗
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.

Aged↗