摘要:

The number and size distribution of β-nerve growth factor (p-NGF) receptor-immunoreactive neurons has been examined in the nucleus of the diagonal band and the anterior, intermediate and posterior regions of the nucleus basalis of Meynert in Alzheimer''s disease (AD) and compared with normal brain. The number of neurons was in general lower in AD, although there was not a statistically significant reduction in any region of the basal nuclei. In some regions, there was an increase in the proportion of small neurons, with a decrease in larger neurons. Cortical choline acetyltransferase activity was found to correlate positively with the number of neurons in all areas of the nucleus basalis. In this group of severely demented AD patients, there was a large number of basal forebrain neurons which expressed β-NGF receptors; β-NGF may, therefore, be of therapeutic value in

ISSN:1420-8008    

DOI:10.1159/000107132

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Magnocellular cholinergic neurons in the nucleus basalis of Meynert (nbM) undergo a profound and selective degeneration in patients with senile dementia of the Alzheimer type (SDAT). We show by in situ hybridization that nerve growth factor (NGF) which promotes the survival of basal-forebrain cholinergic neurons is expressed in hippocampal neurons in SDAT brains at levels not significantly different from those in age-matched controls. In situ hybridization was also used to document the expression of NGF receptor (NGFR) mRNA in magnocellular neurons of the nbM in both SDAT and age-matched control brains. Computerized image analysis of the in situ hybridization results showed that the surviving magnocellular neurons in the nbM of SDAT brains contained 3-fold higher levels of NGFR mRNA compared to age-matched controls. This indicates that in SDAT, the expression of NGFR mRNA is upregulated in magnocellular neurons of the nbM; it further suggests that these neurons respond to exogenously added NGF.

ISSN:1420-8008    

DOI:10.1159/000107133

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Nerve growth factor (NGF) is regarded as an important trophic factor for central cholinergic neurons. It only acts on neurons expressing NGF receptors (NGFR). In this study, the extent of colocalization of NGFR and the cholinergic marker, choline acetyltransferase (ChAT), was examined in the basal forebrain of adult rats. Simultaneous labelling for NGFR and ChAT was accomplished by a specific double-immunofluorescence method. An almost complete colocalization of the two antigens was observed in the regions studied. The extent of double-stained neurons ranged from 89.2% (basal nucleus) and 96.9% (horizontal diagonal band) to 99% (vertical diagonal band) and 100% (medial septum). The remaining single labelled cells were immunopositive for ChAT, and only a negligible fraction of them, 0.2% (basal nucleus) and 0.4% (horizontal diagonal band), displayed NGFR immunoreactivity alone. This result emphasizes the specific relationship between NGF and cholinergic neurons in the basal forebrain. These neurons are projecting to hippocampal and cortical targets and are involved in cognition and memory. Investigations evaluating the applicability of NGF treatment to prevent neuronal degeneration may be encouraged by the finding that NGF obviously plays a very specific role in this system.

ISSN:1420-8008    

DOI:10.1159/000107134

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Rats received either N-methyl-D-aspartic-acid-induced bilateral lesions (50 nmol/l µl/side) of a major forebrain cholinergic nucleus (nucleus basalis of Meynert, nbM) or sham operations. After an approximate 1-month recovery period, all subjects were trained and tested on a one-trial passive avoidance task. Thirty minutes prior to training, half of the subjects in each surgical condition were injected with the serotonergic releasing/depleting agent p-chloroamphetamine (2.5 mg/kg), while the other half of subjects received saline injections. Immediately after training, half of the p-chloroamphetamine-injected and saline-injected subjects in each surgical condition were injected with the cholinesterase inhibitor physostigmine (0.06 mg/kg), while the other half were injected with saline. All animals were tested for retention 72 h following training. Disruption of test performance was seen in (1) saline-injected nbM-lesioned animals; (2) sham animals treated with physostigmine alone, and (3) sham and nbM-lesioned animals treated with either p-chloroamphetamine alone, or with p-chloroamphetamine plus physostigmine. Only nbM-lesioned subjects injected with physostigmine alone exhibited enhanced test performance. Lesions of the nbM produced stern depletions in cortical cholinergic enzyme markers (choline acetyltransferase, CAT, and acetylcholinesterase, AChE). Interestingly, p-chloroamphetamine exaggerated both the CAT and AChE depletions in nbM-lesioned animals. These data were interpreted as providing further evidence in support of the view that the cholinergic and serotonergic systems interact at a cognitive and at a neurochemical level. Implications for the therapeutics of Alzheimer''s disease are discussed

ISSN:1420-8008    

DOI:10.1159/000107135

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

In the first part of the study, a comparison of 19 patients with Alzheimer''s disease (AD) with 19 age-matched controls was performed to establish diagnostic criteria of AD with positron emission tomography and 18F-2-fluoro-2-deoxygIucose. Patients had a mean age of 60.6 ± 7.1 years, and a mean score of 14.5 ± 7.3 in Mini Mental Status examination, and of 4.9 ± 0.9 on the Global Deterioration Scale. They fulfilled current research criteria (NINCDS-ADRDA) for probable AD and had been screened rigorously to exclude other potentially dementing conditions, in particular cerebrovascular disease. Regional glucose metabolism was always abnormal in temporoparietal association areas, at least unilaterally, and in most patients also in fronto-lateral association areas. Regional metabolism relative to whole-brain metabolism was always normal in cerebellum, brain stem, and lentiform nucleus, and in most patients also in visual and sensorimotor cortex. A metabolic ratio of typically affected to typically unaffected regions was designed to represent this characteristic pattern. It provided a complete separation of AD patients from normals. In the second part of the study, the diagnostic power of this ratio was tested in an independent sample of 56 patients with a mean age of 59.9 ± 11.3 years. Eight of these patients had subjective memory complaints, but were found completely normal at neuropsychological and clinical examination. Twenty-two had cognitive deficits due to diseases other than AD, among them 7 with cerebrovascular disease, and 26 had probable AD. The classification by the metabolic ratio as AD or non-AD was correct in 85%, with a sensitivity of 92, and a specificity of

ISSN:1420-8008    

DOI:10.1159/000107136

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Eleven patients with senile dementia of Alzheimer type were treated with acetyl-L-carnitine (ALC) intravenously for 10 days and then orally for 50 days. Serum levels of cortisol and adrenocorticotropic hormone were measured at baseline and after the intravenous treatment. Neuropsychological assessment was also carried out at the same times and at the end of the oral treatment. The results show a trend toward a decrease of the mean cortisol levels and a significant improvement of cognitive performances. These data could support the idea of the neuronotrophic action of ALC, indicating its usefulness for the treatment of dementia disorders.

ISSN:1420-8008    

DOI:10.1159/000107137

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Symptoms of normal-pressure hydrocephalus (NPH) and the complete Klüver-Bucy syndrome (KBS) developed in a previously healthy woman before the appearance of ventricular dilatation on computerized tomography. Ventricular enlargement typical of NPH occurred several months later. Following ventriculoperitoneal shunting, gait abnormalities and KBS resolved, while incontinence, memory, and intellect improved and have since remained stable. An associated sleep disturbance characterized by early onset of rapid-eye movement (REM) sleep periods and sleep spindles throughout REM sleep was also improved by treatment. NPH may impair periventricular function before ventricular dilatation becomes apparent

ISSN:1420-8008    

DOI:10.1159/000107138

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The current assessment of dementia due to vascular causes in terms of terminology, classification, clinical features and diagnostic criteria, neuropathological lesions, risk factors, and possible treatment is reported. The term vascular dementia (VD) covers all syndromes with dementia of vascular origin. The clinical workout may reach a diagnostic sensitivity ranging from 70 to 85%. Verified ischemic lesions associated with dementia include multiple large and small infarctions, multiple lacunes, and, less frequently, watershed infarctions and other vascular diseases. However, the pathological evidence of infarction does not necessarily mean that cerebral vascular lesions are responsible for a state of dementia. The mixed forms (degenerative and vascular dementia) are difficult to assess both from the diagnostic and neuropathological point of view. The etiology of VD is multifactorial.

ISSN:1420-8008    

DOI:10.1159/000107139

出版商:S. Karger AG    

年代:1990

数据来源: Karger