Norihiko Iwamoto

Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections

C-reactive protein (CRP) is a well-known serum protein which increases during inflammation and deposits in damaged tissues. To establish whether CRP appears in brain of Alzheimers disease (AD), we immunohistochemically investigated tissue sections which were pretreated with formic acid. Positive immunostaining by anti-CRP antibodies was clearly recognized in senile plaques (SP) in the pretreated tissue sections, with very weak immunostaining in non-treated sections. These findings may suggest that the formation process of SP includes an acute-phase inflammatory state.

Localization of calpain immunoreactivity in senile plaques and in neurones undergoing neurofibrillary degeneration in Alzheimer's disease

An antibody raised against the calcium activated neutral protease (calpain) was used to investigate the possible involvement of this enzyme in the formation of plaques and tangles in Alzheimer-type dementia (ATD) brain. Our results revealed the presence of a number of strongly stained calpain positive neurones in the normal human cerebral cortex and a loss of calpain positive cells in ATD brain. Furthermore, double staining experiments revealed that calpain immunoreactivity was present in cells undergoing tangle formation, and was also present in senile plaques. These data suggest that activation of calpain may be an important factor in the abnormal proteolysis underlying the accumulation of plaques and tangles in ATD.

First-episode neuroleptic-free schizophrenics: Concentrations of monoamines and their metabolites in plasma and their correlations with clinical responses to haloperidol treatment

Thirty-two first-episode neuroleptic-free schizophrenics were treated with neuroleptics for 8 weeks. The monoamines and their metabolites, dopamine, norepinephrine, serotonin, homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol(MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in plasma were measured to examine the association with treatment responses and psychopathology assessed according to the brief psychiatry rating scale (BPRS). No differences were noted in the pretreatment concentrations of monoamines and their metabolites between patients and healthy controls; however, during treatment the concentrations of HVA and MHPG were significantly reduced only in the schizophrenics who responded to treatment. Moreover, the HVA and MHPG reductions correlated significantly with improvements in BPRS scores. Since their plasma levels reflect to some extent central dopaminergic and noradrenergic activities, respectively, the present findings suggest the involvement of these systems in the pathogenesis of schizophrenia as well as the usefulness of such measurements as predictors of responsiveness to neuroleptics.

Distribution of amyloid deposits in the cerebral white matter of the Alzheimer's disease brain : relationship to blood vessels

Abstract The relationship between blood vessels and amyloid β (Aβ)-protein deposits in the cortex of the Alzheimer’s disease (AD) brain is still controversial. It is difficult to distinguish whether the Aβ deposits are associated with blood vessels or neurons because of their widespread and complicated distribution. In this study, we investigated the distribution of Aβ deposits in the cerebral white matter of the AD brain as a means of removing the bias of neuronal distribution. An immunohistochemical study of 100 serial sections, after pretreatment with formic acid for 24 h, revealed the presence of Aβ deposits in the cerebral white matter of the AD brain. There are various morphological types of plaques containing Aβ deposits in the white matter, the same as in the gray matter. While the majority of Aβ deposits was of a circumscribed type such as “classic” and “primitive” plaques, “compact” and “diffuse” plaques were also observed in the white matter. The location of the Aβ deposits was, for the most part, immediately beneath the gray matter. The distribution of Aβ deposits in the white matter was found to correspond to the orientation of the blood vessels. Serial sections also revealed that these Aβ deposits were distributed along a single blood vessel. These findings suggest that the deposition of Aβ in the cerebral white matter is primarily related to the blood vessels.

Endothelin-1-like immunoreactivity in cerebral cortex of Alzheimer-type dementia

1. Endothelin-1-like immunoreactivity (ET-1-LI) in cerebral cortex in postmortem brains obtained from patients with Alzheimer-type dementia (ATD) was measured by enzyme-immunoassay. 2. The ET-1-LI in the ATD brains was significantly increased in frontal and occipital cortex than those in the control brains and a significant correlation was found between frontal and temporal lobe of ATD brains. 3. These findings may explain the clinico-radiological results that the cerebral blood flow is decreased in ATD patients, the mechanism of which is still unknown.

Demonstration of neurofibrillary tangles in parvalbumin-immunoreactive interneurones in the cerebral cortex of Alzheimer-type dementia brain.

The pathological changes occurring in a population of parvalbumin-like immunoreactive cerebral cortical interneurones in postmortem Alzheimer-type dementia brain tissue were determined by double staining cerebral cortical sections for parvalbumin, tau and/or calpain-like immunoreactivities. By counting the number of double immunostained cells it was determined that 4% parvalbumin and 25% of calpain-like immunoreactive cells showed evidence of tau-like immunoreactivity, indicative of neurofibrillary tangles. These results suggest that cerebral cortical parvalbumin-like immunoreactive neurones are relatively resistant to the pathological changes underlying the formation of neurofibrillary tangles associated with Alzheimer-type dementia.

Assessment of cerebrospinal fluid levels of serum amyloid P component in patients with Alzheimer's disease

Serum amyloid P component (SAP) is a normal plasma constituent that is observed both in senile plaque and in neurofibrillary tangle in brains of patients with Alzheimers disease (AD). In this study, we evaluated the SAP levels in cerebrospinal fluid (CSF) of 72 patients with AD, 11 frontotemporal dementia and nine normal control subjects. There was no significant difference in the SAP levels between the AD group and other groups. However, among AD patients, cognitive function was rated using the Mini-Mental State Examination and was correlated with the SAP level (R = 0.38, P < 0.05). Our results suggest that measurement of the SAP levels in CSF can be useful for assessing the degree of cognitive impairment in AD patients.

Selective loss of calbindin D28K-immunoreactive neurons in the cortical layer II in brains of Alzheimer's disease : a morphometric study

To investigate the relationship between neuronal death and intracellular calcium homeostasis in brains from patients with Alzheimers disease (AD), we quantitatively analyzed morphological changes of calbindin-immunoreactive neurons. Neuronal counts were made in the autopsy brains from 6 control and 6 AD patients. Calbindin-immunoreactive neurons were mainly distributed in cortical layer II and were selectively lost in the AD brains. Further, the number of calbindin-immunoreactive neurons showed a negative correlation with age in the control group. These findings strongly suggest that age-related reduction of calbindin-immunoreactive neurons may be exaggerated in AD brains and change in calcium homeostasis may be involved in the pathogenesis of AD.

Serum Amyloid P Component Level in Alzheimer's Disease

Serum amyloid P component (AP) is a normal plasma constituent that is observed in senile plaques and neurofibrillary tangles in brains of Alzheimers disease (AD) patients. In this study we have evaluated the AP levels in sera of 16 patients with AD and in 16 control subjects by enzyme-linked immunosorbent assay. The AP level was 22.4 +/- (SD) 7.0 micrograms/ml in the AD group and 34.4 +/- (SD) 6.6 micrograms/ml in the control group. The AP level in the AD group was significantly lower than that of the control group (p < 0.01). In the control group, there was no correlation between AP levels and age. Our results suggest that the production of AP by the liver (hepatocytes), thought to be the only source, may be suppressed in AD patients and that the deposition of AP in senile plaques and neurofibrillary tangles is not due to its overproduction.

A juvenile case of frontotemporal dementia: Neurochemical and neuropathological investigations

1. An autopsy case of frontotemporal dementia with onset at the early age of 28 years is reported. 2. The neuropathological features consisted of limited, knife-like frontotemporal atrophy with severe neuronal loss, spongiform change and gliosis, which is compatible with the frontotemporal dementia. 3. Biochemical determinations disclosed that biogenic amines and their metabolites, predominant in the dopaminergic markers, were depleted in the damaged regions. 4. Since biochemical data in frontotemporal dementia are few in previous studies, it will be determined whether these biochemical changes are characteristic for the juvenile type of frontotemporal dementia or not.