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  • Alzheimer's disease  (62)
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  • 1
    ISSN: 1435-1463
    Keywords: Alzheimer's disease ; muscarinic ; receptors ; fibroblast ; amyloid precursor protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have characterised the muscarinic receptor subtypes found in human skin fibroblasts and compared binding levels in cell lines from members of the Alzheimer's disease family with the Swedish amyloid precursor protein (APP) 670/671 mutation. Binding studies with [3H] quinuclidinyl benzilate ([3H]QNB) and the M2/M4 selective antagonist [3H](±)-5,11-dihydro-11-{[(2-[(di-propylamino)methyl]-1-piperidinyl}ethyl)amino]carbonyl}-6H-pyrido(2,3-b)(1,4) benzodiazepine-6-one ([3H]AF-DX 384) revealed the presence of a single population of muscarinic receptors on lysed fibroblast membranes. [3H]QNB binding was displaced by a number of selective muscarinic ligands with a rank order of potency: atropine〉himbacine〉methoctramine〉(±)-p-fluoro-hexahydro-sila-difenidol hydrochloride〉pirenzepine〉muscarinic-toxin-3. APP 670/671 mutation carrying cell lines showed 25–35% lower levels of muscarinic receptors labelled with [3H]QNB, [3H]N-methyl scopolamine and [3H]AF-DX 384, compared to controls. This difference was not statistically significant due to large individual variation. It is concluded that muscarinic receptors on adult skin fibroblasts are predominantly of the M2 subtype. Since these cells do not possess M1 and M3 receptor subtypes, they are unlikely to provide a good model for studying muscarinic receptor regulation of APP processing.
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  • 2
    ISSN: 1435-1463
    Keywords: Spinal cord ; Alzheimer's disease ; choline acetyltransferase ; acetylcholinesterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease.
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  • 3
    ISSN: 1435-1463
    Keywords: Cholecystokinin ; CCK receptors ; Alzheimer's disease ; CCK-4 ; pentagastrin ; cerebral cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in high concentrations and is involved in learning and memory as well as neurodegenerative processes. Cortical brain samples from 9 patients with Alzheimer's disease and 9 matched control cases were studied with respect to the concentrations of various molecular forms of CCK and the CCK receptor binding characteristics. No differences were found between patients and controls in any of these measures. Significant correlations were found between the concentrations of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition, the concentrations of CCK-4 and CCK-5 showed a highly significant and positive correlation.
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  • 4
    ISSN: 1435-1463
    Keywords: Alzheimer's disease ; protein phosphatase ; neuron ; astrocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that activities of the protein phosphatases PP-2A and PP-2B towards the microtubule associated protein tau are reduced in Alzheimer's disease (AD) frontal cortex (Gong et al., 1993, 1995), suggesting that PP-2A and PP-2B are involved in the hyper-phosphorylation of tau in AD. Most recently, we found that protein levels of PP-2A and PP-2B are elevated in postsynaptic supernatant (S2) fractions prepared from AD temporal cortex, and that the activities of these enzymes were not significantly different between AD and control cases (Pei et al., in press). In the present study, we found that astroglia positive for PP-2A and PP-2B immunoreactivities were greater in numbers in AD medial temporal cortex, compared to controls. GFAP levels, as determined by indirect ELISA, were approximately 1.5 times greater in the P1 (500 × g) fraction from AD temporal cortex, compared to controls. GFAP levels in the P1 fraction showed significant correlations with PP-2A and PP-2B levels in the postsynaptic S2 (20,000 × g) fraction from the same brains. These results suggest that astrogliosis probably accounts for the increased levels of PP-2A and PP-2B in the S2 fraction in AD brain and that the levels of these enzymes per neuron are likely to be decreased.
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  • 5
    ISSN: 1435-1463
    Keywords: Alzheimer's disease ; alpha-tocopherol ; vitamin E ; cerebrospinal fluid levels ; serum levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 44 apparently well-nourished patients with Alzheimer's disease (AD) and 37 matched controls. CSF and serum vitamin E levels were correlated, both in AD patients and in controls. The mean CSF and serum vitamin E levels were significantly lower in AD patients, and the CSF/serum ratio of AD patients did not differ significantly between the 2 study groups. CSF vitamin E levels did not correlate with age, age at onset, duration of the disease and score of the Minimental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that low CSF and serum vitamin E concentrations in AD patients could be related with a deficiency of dietary intake of vitamin E.
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  • 6
    ISSN: 1435-1463
    Keywords: Keywords: Amyloid ; marmoset ; non-human primate ; Alzheimer's disease ; aging ; senile plaques ; cerebrovascular amyloid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Cerebral β-amyloid occurs in elderly animals of some species and in Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally with brain tissue from a patient with Alzheimer's disease. Six years later, when the monkeys were middle aged, we found moderate numbers of intracerebral plaques and cerebrovascular deposits containing β-amyloid. We have re-examined these brains and those of 10 other marmosets injected with brain homogenate containing β-amyloid, and have found some β-amyloid in animals injected more than 4 years previously. We have found β-amyloid in 4 of 26 elderly control marmosets, but not in 9 young to middle-aged control marmosets. The β-amyloid found in middle aged marmosets injected with Alzheimer brain tissue was, therefore, not a consequence of their age. Deposits in large cerebral vessels in elderly marmosets, and in marmosets previously injected with brain tissue containing β-amyloid, reacted with antibodies to Aβ and Aβ1-40; plaques and microvessel deposits reacted with antibodies to Aβ and Aβ1-42.
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  • 7
    ISSN: 1435-1463
    Keywords: Keywords: Nitric oxide ; nitrite ; nitrate ; Alzheimer's disease ; vascular dementia ; cerebrospinal fluid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The concentration of the nitric oxide (NO) metabolites nitrite (NO2 −) and nitrate (NO3 −) in the cerebrospinal fluid from patients with Alzheimer's disease (AD), vascular dementia of the Binswanger type (VDBT) or multiple small infarct type (MSID), and controls were determined using high performance liquid chromatography. The nitrite concentration was significantly higher in VDBT/MSID patients than in controls (p 〈 0.005). The nitrate concentration and the combined nitrite and nitrate concentration was significantly higher in both AD (p 〈 0.05) and VDBT/MSID (p 〈 0.001) patients than in controls, with these concentrations being significantly greater in VDBT/MSID than AD patients (p 〈 0.005). The combined nitrite and nitrate concentration significantly decreased as the severitry of dementia progressed in AD (rs = 0.70, p 〈 0.01), but remained elevated in all stages of VDBT/MSID. These results suggest that NO production or oxidation in the brain increases in the early stage of AD and then decreases as neuronal cell loss progresses, but increases throughout the course of disease in VDBT/MSID, which may in part contribute to neuronal degeneration in both conditions.
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  • 8
    ISSN: 1435-1463
    Keywords: Keywords: Cognitive impairment ; Alzheimer's disease ; biochemical markers ; one-carbon-metabolism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. In dementia disorders, it can be assumed that the pathological process in the brain has been present for a long time. It is therefore of importance to have a preclinical or an early clinical diagnosis. Obviously, vulnerability genes, such as ApoE-4, can be diagnosed preclinically. As we have no treatment to offer patients with genetic risk factors, genotyping for ApoE-4 is at present of no clinical use. Trained neuropsychologists have today access to sensitive tests which reveal cognitive impairment before the disturbances reach the level of dementia. Laboratory investigations of cerebrospinal fluid have so far yielded no great results. Tau protein appears to be the most sensitive marker, but it is unspecific. Chromogranin A separates early onset from late onset Alzheimer's disease and seems to be a marker for synaptic degeneration. Synaptotagmin was also found to be reduced in patients with early onset Alzheimer's disease. Still we do not know, however, whether these proteins are early markers for degenerative processes in the brain. Laboratory investigations of blood have not yielded markers of use in early or differential diagnosis of dementia disorders. In a study at our own institute, however, we found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism.
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  • 9
    ISSN: 1435-1463
    Keywords: Keywords: Lamotrigine ; glutamate ; glutamate release ; excitatory neurotransmitter ; Alzheimer's disease ; neuroprotection ; therapy .
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. It has been proposed that excitotoxic damage by glutamatergic hyperactivity is responsible for neurodegeneration in Alzheimer's disease. Lamotrigine (LTG) inhibits presynaptic glutamate release and is considered to be effective in treatment of other neurodegenerative disorders by its cerebroprotective properties. We used LTG in 11 patients with the diagnosis of probable Alzheimer's disease. 300 mg/day administration of LTG improved word recognition, naming and depressed mood on Alzheimer Disease Assessment Scale (ADAS).
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  • 10
    ISSN: 1435-1463
    Keywords: Keywords: Homocysteine ; dementia ; Alzheimer's disease ; vascular dementia ; folic acid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Hyperhomocysteinemia is a strong risk factor for atherosclerotic vascular disease, and elevated serum homocysteine is correlated with vitamin B deficiency. In this pilot study, significantly elevated homocysteine levels were found in patients with Alzheimer's disease as well as in patients with vascular dementia, probably indicating similar pathophysiological pathways. We found significant correlations between low folic acid concentrations as well as high homocysteine concentrations and cognitive decline. Supplementation with folic acid may be an inexpensive way to reduce elevated homocysteine levels in demented patients.
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