Contradictory results have been reported on the downregulation and role of the brain-specific protein metallothionein-III (MT-III, GIF) in Alzheimer disease (AD). In this article, the importance of MT-III downregulation in AD brain was re-evaluated in temporal and frontal cortex, hippocampus, and cerebellum of 11 AD patients and two groups of five and six control subjects, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the levels of MT-III mRNA relative to the levels of three constitutive RNAs: beta-actin, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), and ribosomal RNA 18S (rRNA 18S). The distribution of MT-III was similar to that of each of the three constitutive RNAs. The relative levels of each of these RNAs was high in brain regions examined in both AD patients and control subjects. Our findings do not support a downregulation of MT-III mRNA in the frontal cortex as well as the temporal cortex and hippocampus of AD patients. However, the level of MT-III mRNA was not constant in the investigated samples, suggesting that MT-III mRNA regulation could be controlled by factors other than AD pathology. Brain-derived neurotrophic factor (BDNF) mRNA levels were hardly detectable by RT-PCR in human brain tissue; a trend for a decrease was apparent in the temporal cortex of AD patients. In conclusion, the content of MT-III mRNA in the brain of AD patients was not detectably impaired, whereas BDNF mRNA may be affected.

Actins↗

PubMedDate not supplied

alpha 2-Macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease.

Because it has been suggested that alpha 2M could be involved in the generation of amyloid peptide, attention was given to a possible association of alpha 2M expression and amyloid accumulation in the brain. Therefore, we investigated the presence of the proteinase inhibitor alpha 2-macroglobulin (alpha 2M) in the cerebra of 4 patients with Alzheimer's Disease (AD). One case of a patient with Down's syndrome, 2 cases of patients with Dementia of the Lewy Body type (DLB), 1 case of an aged, clinically nondemented person who displayed many amyloid plaques, and 3 normal aged control brains were also studied. The results obtained by immunocytochemistry with monoclonal antibodies directed against two different epitopes of human alpha 2M showed an association of alpha 2M, only with neuritic-type plaques in patients with AD. No alpha 2M immunoreactivity was found in either preamyloid-type plaques or burned out-type plaques in AD, DLB, or aged nondemented controls. The results do not support a direct role of this proteinase inhibitor in the formation of amyloid. Because alpha 2M is observed to be associated with reactive microglia in the outer border of the neuritic plaques, the data suggest that alpha 2M could be a marker for an inflammatory cellular process in these neuritic plaques.

Aged↗

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NADPH-diaphorase-containing neurons in cortex, subcortical white matter and neostriatum are selectively spared in Alzheimer's disease.

To investigate the involvement of NADPH-diaphorase (NADPH-d)-containing neurons in Alzheimer's disease (AD), NADPH-d enzyme histochemistry in vibratome sections was applied to the superior frontal and superior temporal cortex and the neostriatum in 5 AD and 6 aged control brains. Overall there was a neuronal loss and atrophy in the cortex of AD. Despite slight morphological neuronal changes in the cortex of AD, we found no significant difference in the number of NADPH-d-positive neurons in both cortex and neostriatum between control and AD cases. These results provide further evidence for a selective preservation of NADPH-d neurons in AD. In order to check whether nNOS-immunoreactive neurons are identical to NADPH-d-positive neurons in the human brain, we examined the frontal and temporal cortex and neostriatum of normal human brains in serial cryostat sections. We found that nNOS-containing neurons paralleled NADPH-d-positive neurons in these brain regions. Copyrightz1999S.KargerAG,Basel

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Amyloid precursor protein accumulation in Lewy body dementia and Alzheimer's disease.

The presence of amyloid precursor protein (APP) and beta-amyloid protein (beta A4) was investigated in the cerebra of 4 patients with Alzheimer's disease (AD), 1 patient with Down's syndrome, 4 patients with dementia of the Lewy body type (DLB) and 4 age-matched, clinically nondemented controls, of which one displayed many amyloid plaques. The different types of amyloid plaques stained strongly with antibodies against beta A4. Antibodies against the C-terminal region of APP reacted only weakly with small swollen neurites and with globular deposits in neuritic-type plaques from patients with AD. The antibody against the N-terminal region of APP stained strongly cellular elements in the neuritic type plaques of patients with AD but not dense cored plaques. In contrast, patients with DLB displayed with this antibody a homogeneous staining of dense cored amyloid plaques. Some Lewy bodies stained with the antibody against the N-terminal region of APP as well. These results indicate that the processing of APP in AD and DLB could be different, to yield different fragments deposited in AD and DLB amyloid plaques.

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PubMedDate not supplied

Heparan sulfate expression patterns in the amyloid deposits of patients with Alzheimer's and Lewy body type dementia.

Heparan sulfate (HS), along with serum amyloid P component, has been identified in all types of amyloid investigated so far, regardless of the type of amyloid protein deposited. To assess whether unique or specific HS proteoglycans (HSPGs) may be involved in the formation of these lesions, we have investigated the accumulation of several distinct HSPG epitopes in the cerebra of patients with different forms of neurodegenerative disease. A panel composed of several antibodies revealed distinctive patterns of HSPG accumulation. In patients with dementia of the Lewy body type, the burned-out-type plaques and preamyloid-type plaques were strongly stained by both the anti-HS 'chain' and anti-HS 'stub' antibodies, but by none of the available anti-core protein antibodies. In Alzheimer's disease, the preamyloid-type plaques, dense-cored-type plaques, neuritic-type plaques and the neurofibrillary tangles were stained by the anti-'stub' antibody. The anti-'chain' and the anti-core protein antibodies, in contrast, failed to stain the preamyloid-type plaques and burned-out-type plaques, but stained the neuritic-type plaques in these patients. These data suggest differences in the types of HS and HSPG (fragments) that accumulate in amyloid lesions that may hallmark neurodegenerative disorders of different etiologies.

Aged↗

PubMedDate not supplied

Maintenance therapy of chronic psychostic patients with a weekly oral dose of R 16 341. A controlled double-blind study.

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Adult↗

PubMedDate not supplied

The interaction between neuroleptic treatment and sociotherapeutic approach in chronic schizophrenics. Investigations with haloperidol, penfluridol and pimozide.

In the modern treatment of chronic schizophrenic patients two major trends can be outlined: sociotherapy and psychopharmacotherapy. Therefore it is an important question whether these two therapeutic approaches interact in a positive or a negative way. Selected examples of experiments about the interaction of haloperidol, penfluridol and pimozide with sociotherapy are given and discussed. It is also demonstrated that the learning capacity of the patients depends on the particular type of neuroleptic.

Community Psychiatry↗