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Biomedical subjects

D Neary

Publications and source records attributed to D Neary.

At least 91 records · Page 5Linked to original sources
PubMed1987

DNA repair in lymphocytes from young and old individuals and from patients with Alzheimer's disease.

Lymphocytes from patients with ataxia telangiectasia and Down's syndrome show a greater frequency of chromosome aberrations after ionising radiation than do lymphocytes from normal people. The connection between Down's syndrome and Alzheimer's disease (AD) is well-known. In view of this and of a study showing a greater sensitivity of AD than of normal lymphoblastoid cells to X-irradiation (measured by viability), we have examined repair of AD lymphocytes (hydroxyurea-treated) by measuring [3H]thymidine incorporation after gamma-irradiation. We have found no difference in incorporation between AD and normal lymphocytes from age-matched individuals. However, incorporation decreases with age in gamma-irradiated cells and to a lesser extent in unirradiated cells.

Adult↗
PubMed1987

Cholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

Acetylcholinesterase (AChE) and nonspecific cholinesterase (nsChE) activities of lumbar ceresbrospinal fluid (CSF) from patients with a clinical or histological diagnosis of Alzheimer's disease have been compared with those of normal age-matched control patients and patients with dementia of non-Alzheimer aetiology. No significant differences in the AChE activity of lumbar CSF from histologically and clinically diagnosed Alzheimer's disease patients and normal age-matched controls were found, although they could be distinguished from controls and other dements by their lower lumbar CSF levels of nsChE activity and by their elevated ratio of AChE/nsChE. A lower level of AChE activity was observed in the lumbar CSF of patients with dementia of non-Alzheimer aetiology. The AChE and nsChE activities of ventricular CSF obtained at postmortem have also been examined. The AChE activity of the ventricular CSF of patients with histologically confirmed Alzheimer's disease was 66% lower than that of age-matched controls; these patients could also be distinguished from normals by their lower levels of nsChE and by the elevated ratio of AChE/nsChE activities. A molecular defect in the AChE in the ventricular CSF of Alzheimer patients is indicated by the finding that the enzyme failed to show inhibition by high concentrations of substrate. The lower level of AChE in ventricular CSF may reflect the changes in this enzyme in forebrain regions of Alzheimer patients. Although it is at present not possible to correlate the lower levels of nsChE found in CSF with any known brain pathology, the significantly altered ratio of AChE/nsChE activities in lumbar CSF may possibly form the basis for a diagnostic test of Alzheimer type dementia.

Acetylcholinesterase↗
PubMed1987

Presynaptic serotonergic dysfunction in patients with Alzheimer's disease.

Indices of presynaptic serotonergic nerve endings were assayed in neocortical biopsy samples from patients with histologically verified Alzheimer's disease. The concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid, serotonin uptake, and K+-stimulated release of endogenous serotonin were all found to be reduced below control values. Changes occurred in samples from both the frontal and temporal lobes, but they were most severe (at least a 55% reduction) in the temporal lobe. This is indicative of substantial serotonergic denervation. Values for serotonergic markers in Alzheimer's disease samples did not show correlations with rating of the severity of dementia, indices of cholinergic innervation, or senile plaque and cortical pyramidal neurone loss. However, neurofibrillary tangle count and an index of glucose oxidation (both probably reflecting pyramidal cells) correlated with the concentration of 5-hydroxyindoleacetic acid.

Alzheimer Disease↗
PubMed1987

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy.

Aged↗
PubMed1986

Cerebral biopsy in the investigation of presenile dementia due to cerebral atrophy.

Investigation by cerebral biopsy of patients with dementia associated with cerebral atrophy permits the examination of clinico-pathochemical relationships, and provides a means of distinguishing and classifying forms of cerebral atrophy. Benefits of the procedure must however be weighed against possible adverse effects of surgical intervention. The study examines the outcome following biopsy of 24 patients with presenile dementia. No major operative complications were encountered, and recovery was uneventful in all but a single patient. The relevance of the findings to the study of dementia by cerebral biopsy is discussed.

Aged↗
PubMed1986

Neuropsychological syndromes in presenile dementia due to cerebral atrophy.

In a prospective study of 24 patients with presenile dementia associated with cerebral atrophy, clinical and psychological characteristics of patients' disorder were examined in relation to pathological and chemical findings obtained from tissue analysis following cerebral biopsy. The histological features of Alzheimer's disease were found in 75% of cases, but not in 25%. Distinctive patterns of neuropsychological breakdown emerged allowing clinical grouping of patients. While clinical patterns were helpful in differentiating Alzheimer's disease from non-Alzheimer's disease, there was not an absolute concordance between clinical and patho-chemical groupings. The findings, which support the notion that the "cerebral atrophies" represent a heterogeneous group of conditions, have relevance for the clinical diagnosis of presenile dementia.

Aged↗
PubMed1986

Alzheimer's disease: a correlative study.

In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of large cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex.

Acetylcholine↗
PubMed1985

Neurochemical studies of early-onset Alzheimer's disease. Possible influence on treatment.

Multiple neurotransmitter deficits found in recent autopsy studies of patients with Alzheimer's disease may militate against the success of "simple cholinergic replacement" as treatment. To study acetylcholine synthesis, we measured the incorporation of radiolabeled glucose into the transmitter in temporal-cortex specimens obtained at diagnostic craniotomy in 17 young patients with Alzheimer's disease. Synthesis of acetylcholine was significantly correlated with cognitive impairment. These results are consistent with the view that the deficit in the presynaptic cholinergic system is a relatively early change in the development of the clinical features of the disease. Other alterations in noradrenergic cells, some cortical neurons, postsynaptic cortical receptors, and possibly serotoninergic cells may not be closely associated with Alzheimer's disease.

Acetylcholine↗
PubMed1985

Putative amino acid transmitters in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia.

Concentrations of individual free amino acids were determined in lumbar cerebrospinal fluid (CSF) from patients with various complaints including histologically verified Alzheimer's dementia. Glycine and glutamine in the CSF of Alzheimer's dementia samples were lower than that of control samples. Only the concentration of glutamic acid in Alzheimer's dementia patients correlated with psychological measures. The reduction in glycine concentration was not specific for Alzheimer's dementia.

Adult↗
PubMed1984

Somatostatin-like immunoreactivity in lumbar cerebrospinal fluid from neurohistologically examined demented patients.

The concentration of somatostatin-like immunoreactivity (SLI) in lumbar cerebrospinal fluid was measured in clinically suspected examples of either Alzheimer's disease (AD) or Pick's disease and controls. No significant correlation was found between the concentration of SLI and the age (22-73 years) of controls. Histological examination of brain material from the demented patients enabled the samples to be divided into AD and examples of clinically suspected AD or Pick's disease without specific histological change. The mean concentration of SLI was only slightly reduced in patients with AD in the presenium compared to control, and was unaltered from control in the examples of AD of senile age. The group of demented patients without specific histological change had a reduced concentration of SLI in lumbar CSF compared to control patients.

Age Factors↗
PubMed1984

Monoamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia.

Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxy indoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) from control subjects and patients of both presenile and senile age with histologically verified Alzheimer's dementia. CSF HVA increased with age in control but not in Alzheimer patients. HVA and 5-HIAA in the CSF of presenile Alzheimer patients was lower than that of age matched control subjects.

Aged↗
PubMed1983

Amino acid release from biopsy samples of temporal neocortex from patients with Alzheimer's disease.

Tissue prisms prepared from neurosurgical samples of temporal neocortex of Alzheimer and control patients, upon depolarization preferentially released aspartate, glutamate and gamma-aminobutyrate (GABA). The Alzheimer and control samples did not significantly differ in the pattern of amino acid release, although acetylcholine synthesis by the Alzheimer tissue prisms was greatly reduced. There was no correlation between the efflux of any amino and acetylcholine synthesis. These observations suggest that in Alzheimer's disease there are no major changes in the extracellular concentrations of these putative amino acid transmitters.

Acetylcholine↗
PubMed1983

Metabolic processes in Alzheimer's disease: adenine nucleotide content and production of 14CO2 from [U-14C]glucose in vitro in human neocortex.

Samples of neocortex removed at diagnostic craniotomy from patients with Alzheimer's disease and incubated in vitro showed an increased production of 14CO2 from [U-14C]glucose compared with neurosurgical controls. This was a feature of incubations in the presence of both 5 mM K+ (142% control) and 31 mM K+ (126%). Specific labelling of the amino acid pool was unaltered, suggesting that the apparent increase of CO2 production was not merely a reflection of changes in dilution of the radiolabel from glucose. The content of adenine nucleotides was significantly less than control values in the tissue from patients with Alzheimer's disease after in vitro incubations but the adenylate energy charge was unchanged, indicating that normal energy metabolism was not grossly impaired in these preparations.

Acetylcholine↗
PubMed1983

Presynaptic cholinergic dysfunction in patients with dementia.

Indices of presynaptic cholinergic nerve endings were assayed in neocortical biopsy samples from patients with presenile dementia. For those patients in whom Alzheimer's disease was histologically confirmed, [14C]acetylcholine synthesis, choline acetyltransferase activity and choline uptake were all found to be markedly reduced (at least 40%) below mean control values. The changes occurred in samples from both the frontal and temporal lobes and for [14C]acetylcholine synthesis the decrease was similar under conditions of high and low neuronal activity (as assessed by incubations in 31 mM and 5 mM K+ respectively). Samples from other demented patients, in whom the histological features of Alzheimer's disease were not detected, produced values for all three biochemical parameters which were similar to controls. For the total group of patients with presenile dementia there were correlations between values for the three markers of presynaptic cholinergic nerve endings suggestive of a loss of functional activity at these sites in Alzheimer's disease.

Acetylcholine↗
PubMed1983

Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease.

Markers of serotonin synapses in entire temporal lobe and frontal and temporal neocortex were examined for changes in Alzheimer's disease by use of both neurosurgical and autopsy samples. Uptake of [3H]serotonin, binding of [3H]imipramine, and content of indolamines were all significantly reduced, indicating that serotonin nerve terminals are affected. Binding of [3H]serotonin was also reduced, whereas that of [3H]quinuclidinyl benzilate, [3H]muscimol, and [3H]dihydroalprenolol were unaltered. When the Alzheimer's samples were subdivided according to age, the reduction in [3H]serotonin binding was a feature of only autopsy samples from younger patients. In contrast, presynaptic cholinergic activity was reduced in all groups of Alzheimer's samples, including neurosurgical specimens. Five markers, thought to reflect cerebral atrophy, cytoplasm, nerve cell membrane, and neuronal perikarya were measured in the entire temporal lobe. In Alzheimer's disease the reductions (mean 25%, range 20-35%) were thought to be too large to be due only to loss of structures associated with the presumed cholinergic perikarya in the basal forebrain and monoamine neurones in the brain stem.

Acetylcholine↗