摘要:

Primary neuronal cell cultures from P6 mice were investigated in order to study amyloid protein precursor (APP) gene expression in differentiating neurons. Cerebellar granule cells which strongly express APP 695 allowed the identification of three distinct isoforms of neuronal APP 695. The high-molecular-weight form of APP 695 is sialylated. The expression pattern of neuronal APP 695 changes during in vitro differentiation. Sialylated forms become more abundant upon longer cultivation time. The secreted forms of sialylated, neuronal APP 695 are shown to comigrate with APP isolated from cerebrospinal fluid. We suggest that the different sialylation states of APP 695 may reflect the modulation of cell-cell and cell-substrate interactions during in vitro differentiation and regeneration.

ISSN:1420-8008    

DOI:10.1159/000107337

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

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.

ISSN:1420-8008    

DOI:10.1159/000107338

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer''s disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65–75 years) and 15 AD patients (age 61–78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 (µg/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 ± 0.2, 0.8 ± 0.2 and 0.9 ± 0.2 µg/1). IGF-I levels were lower (p < 0.005) in elderly (73.9 ± 8.2 µg/1) and in AD subjects (108.0 ± 5.9 µg/l) than in young subjects (288.7 ± 22.1 µg/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 ± 49.2 µg/l/h) and in AD subjects (437.6 ± 93.5 µg/l/h) were lower (p < 0.01) than in young subjects (658.6 ± 100.1 µg/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 ± 222.4 and 1,070.3 ± 207.2 µg/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 ± 245.6 µg/l/h). ARG potentiated the GHRH-induced GH rise both in elderly and in AD subjects (1,545.2 ± 246.0 and 1,659.3 ± 196.8 µg/l/h,p < 0.001) but in this case, the GH response to GHRH + ARG overlapped with that in young subjects (2,140.2 ± 229.5 µg/l/h). In contrast to young subjects, in elderly and in AD subjects, the potentiating effect of ARG on GHRH-induced GH rise was higher (p < 0.01) than that of PD. These results show that testing neural controls of GH secretion with different neuroactive substances does not allow to differentiate normal aging from AD. In both groups, somatotroph responsiveness to GHRH is potentiated by the enhancement of the cholinergic activity but much more by ARG, which is compatible with the presenc

ISSN:1420-8008    

DOI:10.1159/000107339

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In order to investigate neuropsychological differences in patients with mild AD, we carried out a pilot study on 28 patients with a clinical diagnosis of mild dementia (CDR: 0.5–1) using an extensive neuropsychological battery, in comparison with 28 normal controls. The results of a cluster analysis, applied on the neuropsychological variables, showed the existence of at least two main subgroups of patients. Cluster 1 patients had a mean age of 61.1 years and showed a greater impairment on measures of language, abstract reasoning and verbal fluency; cluster 2 patients, with a mean age of 72.0, had more severe impairment in memory function. These preliminary results may suggest the existence of different subtypes of AD characterized by selective neuropsychological deterioration in the early stages of the diseas

ISSN:1420-8008    

DOI:10.1159/000107340

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

408 elderly primary care attenders were screened using the Geriatric Depression Scale (GDS) and the 30-item General Health Questionnaire (GHQ). 36% were identified as ''cases'' on the GDS and 32% on the GHQ. The ''cases'' and a random sample of ''non-cases'' were interviewed using the Geriatric Mental State Examination (GMS), the Bedford College Life Events and Difficulties Interview (LEDS), the National Adult Reading Test (NART), and systematic inquiry concerning physical health. Sensitivity and specificity of the GDS were 85% and 68%, and of the GHQ 77% and 67%. General practitioner identification of cases showed a sensitivity of 78% and a specificity of 60% against the GMS. Depression was significantly associated with life events, chronic difficulties, poor physical health and current lack of a confiding relationship. Subjective complaints of depression were associated with low premorbid intelligence and lifelong lack of a confiding relationship. The availability of a confiding relationship appears to have a protective effect against depressive illness associated with life events and chronic difficulties.

ISSN:1420-8008    

DOI:10.1159/000107341

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We reconstructed three-dimensional (3D) surface images from data from single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]-iodoamphetamine (123I-IMP) in 29 patients with Parkinson''s disease, 16 patients with Alzheimer''s disease and 11 normal control subjects. In patients with nondementing Parkinson''s disease, perfusion defects were frequently found in the parietal cortical region at a threshold value of 65%. In demented Parkinson''s disease patients, perfusion defects were frequently noted at threshold of 45–65 %, and were more marked in the bilateral temporal and parietal cortices. In Alzheimer''s disease, perfusion defects were similar to those found in dementing Parkinson''s disease. These results suggest that dementia in Parkinson''s disease is related to the perfusion reduction of the temporoparietal cortex, and may support the view that Parkinson''s disease and Alzheimer''s disease overlap in some patients. A 3D display of an 123I-IMP brain tomogram may be useful for detecting cortical lesions in patients with dementia or cognitive impairmen

ISSN:1420-8008    

DOI:10.1159/000107342

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

It is generally accepted that presenile Alzheimer''s disease (AD) has faster progression and severer clinical manifestation than senile onset AD. Recently a relative left frontal hypoperfusion was only found in patients with presenile AD by using SPECT imaging. The aim of the present report was to ascertain whether the same conclusion could be drawn matching the population with respect to the severity of the cognitive profile and disease duration. Twenty subjects for each group were studied with SPECT and no differences emerged between groups. It is postulated that presenile and senile onset AD represent aspects of the same biological process.

ISSN:1420-8008    

DOI:10.1159/000107343

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The stunning accumulation of data on the physiopathology of Alzheimer''s disease is a real hindrance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cumbersomeness and cost of clinical trials in that field, a review of potential targets for drugs that are supposed to be active against the disease has become necessary, for a true definition of the rational justifications of trials to be envisaged.

ISSN:1420-8008    

DOI:10.1159/000107344

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000107345

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000107346

出版商:S. Karger AG    

年代:1993

数据来源: Karger