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Biomedical subjects

D Neary

Publications and source records attributed to D Neary.

At least 73 records · Page 4Linked to original sources
PubMed1992

Deposition of amyloid beta protein in non-Alzheimer dementias: evidence for a neuronal origin of parenchymal deposits of beta protein in neurodegenerative disease.

In two elderly patients with frontal lobe dementia and in two others with progressive aphasia an inverse relationship between the severity of beta protein deposition and the principal pathology of these disorders was noted. Deposition of beta protein occurred only in areas of cortex where functional (viable) neurones were still present and was absent where neuronal decimation had taken place. Such findings suggest that the presence of functional neurones is necessary for beta protein deposition to occur and, therefore, that neurones may be the source of the amyloid protein that is deposited within brain parenchyma not only in these disorders but also in other conditions, particularly Alzheimer's disease.

Aged↗
PubMed1990

Semi-automatic quantification of regional cerebral perfusion in primary degenerative dementia using 99m technetium-hexamethylpropylene amine oxime and single photon emission tomography.

A new semi-automatic method for quantifying regional cerebral uptake of 99m technetium-hexamethylpropylene amine oxime (99mTc-HMPAO) was used to assess single photon emission tomograms from 5 normal subjects, 14 patients with Alzheimer's disease, 14 patients with dementia of frontal lobe type and 4 patients with dementia with motor neurone disease. Uptake in both posterior cortical regions, although not in other regions, was significantly lower (P less than 0.05) in Alzheimer's disease than in normal controls. Conversely in both dementia of frontal lobe type and dementia with motor neurone disease, uptake was significantly reduced (P less than 0.05) compared with controls in all anterior cortical regions but not in posterior regions. Numerical findings in each disease mirrored the pattern of reduced tracer uptake previously reported by visual assessment. Nine patients were re-examined after an interval of at least 1 year. Comparison of follow-up scans with original images showed significant decreases in mid-anterior, left anterior and left posterior cortical uptake (P less than 0.01) in patients with Alzheimer's disease and in left middle, left posterior and right posterior cortical uptake (P less than 0.01) in patients with dementia of frontal lobe type. The method of quantification may be a useful adjunct to the visual assessment of single photon emission tomograms.

Alzheimer Disease↗
PubMed1990

Ante mortem cerebral amino acid concentrations indicate selective degeneration of glutamate-enriched neurons in Alzheimer's disease.

There is little information about major constituents of the brain in Alzheimer's disease. In the case of amino acids most of the previous data are contradictory. These have been interpreted in an anatomic and neurotransmitter as well as a metabolic context. To help clarify this, the contents of 14 amino acids and ethanolamine were determined in samples of neocortex from diagnostic craniotomies of 15 demented patients (10 with Alzheimer's disease) and other neurosurgical procedures (57 patients, 18 with intractable depression). A comprehensive survey of the effects of possible complicating factors on the concentrations of amino acids showed that artefacts were few; this was in contrast to a post mortem series of brains (16 with Alzheimer's disease and 16 controls; six regions assayed). We have used the ante mortem data to provide the basis for an accurate comparison of amino acid values between Alzheimer and control samples. In Alzheimer's disease, the mean contents of many amino acids were slightly higher (sum of the increases of those significantly affected was 15 nmol/mg protein) whereas glutamate content alone was significantly reduced (by 16 nmol/mg protein). This was not a feature of depression or a group of patients with other dementias. Glutamate content of Alzheimer samples was related to pyramidal neuron density in cortical layer III. These alterations were detected relatively early during the course of Alzheimer's disease and are considered to be due to loss of corticocortical glutamatergic association pathways.

Alzheimer Disease↗
PubMed1990

Frontal lobe dementia and motor neuron disease.

Four patients are described, in whom a profound and rapidly progressive dementia occurred in association with clinical features of motor neuron disease. The pattern of dementia indicated impaired frontal lobe function, confirmed by reduced tracer uptake in the frontal lobes on single photon emission computed tomography (SPECT). Pathological examination of the brains of two patients revealed frontal-lobe atrophy, with mild gliosis and spongiform change. The spinal cord changes were consistent with motor neuron disease. The clinical picture and pathological findings resembled those of dementia of frontal-lobe type and were distinct from those of Alzheimer's disease. The findings have implications for the understanding of the spectrum of non-Alzheimer forms of primary degenerative dementia.

Adult↗
PubMed1989

Characteristics of lymphocyte chromatin from Alzheimer's disease patients and from young and old normal individuals.

We have examined chromatin in lymphocytes from patients with Alzheimer's disease (AD) and from normal individuals of a range of ages. We have found that the neucleosome repeat length does not vary with age for normal individuals over the range 24-78 years and that there is no difference between the value for AD cells (mean and standard deviation, 202 +/- 7 base pairs, bp) and for normals (207 +/- 5 bp). The rate of digestion of chromatin in lymphocyte nuclei by micrococcal nuclease does not appear to differ significantly between old and young normals and AD patients.

Adult↗
PubMed1988

The use of [99mTc]-HM-PAO in the diagnosis of primary degenerative dementia.

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]-HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

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PubMed1988

Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease.

Excitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (less than 3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate-activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+-dependent uptake of D-[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neurotransmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain.

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PubMed1988

Dementia of frontal lobe type.

A significant proportion of patients with presenile dementia due to primary cerebral atrophy do not have Alzheimer's disease. One form of non-Alzheimer dementia may be designated as dementia of frontal lobe type (DFT), on the basis of a characteristic neuropsychological picture suggestive of frontal lobe disorder, confirmed by findings on single photon emission tomography. The case histories of seven patients exemplify the disorder: a presentation of social misconduct and personality change, unconcern and disinhibition, in the presence of physical well-being and few neurological signs. Assessment revealed economic and concrete speech with verbal stereotypes, variable memory impairment, and marked abnormalities on tasks sensitive to frontal lobe function. Visuo-spatial disorder was invariably absent. Comparisons of DFT and Alzheimer patients revealed qualitative differences in clinical presentation, neurological signs, profile of psychological disability, electroencephalography, single photon emission tomography and demography. DFT, which may represent forms of Pick's disease, may be more common than is often recognised.

Alzheimer Disease↗
PubMed1987

Mitochondrial function in brain tissue in primary degenerative dementia.

Previous in vitro and in vivo studies of the brain in Alzheimer's disease indicated alterations in metabolism related to energy production although the relationships between these changes remains obscure. To help resolve this issue, in vitro oxygen uptake by homogenates of fresh samples of frontal neocortex from patients with dementia and neurosurgical controls has been examined as a measure of energy-related metabolism and mitochondrial function. Maximal respiratory rates (measured in the presence of an uncoupling agent) were similar for samples from 7 controls, 5 patients with Alzheimer's disease and two patients diagnosed clinically as Pick's disease, suggesting that there was little or no effect of these dementias on the maximal metabolic capacity of the tissue. However, under some conditions producing sub-maximal metabolic activity (which are of potentially greater physiological relevance) oxygen uptake rates were significantly elevated in the dementia group. The ratio of oxygen uptake rates in the presence and absence of ADP was significantly reduced (to 58% of control; P less than 0.02) for the dementia patients compared with controls, possibly indicative of partial mitochondrial uncoupling. These results indicate metabolic changes expressed in vitro which may be relevant to the pathogenesis of Alzheimer's disease and some related dementias.

Alzheimer Disease↗
PubMed1987

Catecholaminergic neurones assessed ante-mortem in Alzheimer's disease.

Indices of dopaminergic and noradrenergic varicosities were assayed in neocortical tissue obtained at diagnostic craniotomy from patients with Alzheimer's disease in the presenium. Dopaminergic markers (concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid) were not significantly different from controls in either frontal or temporal cortex. In the frontal cortex, the release of endogenous dopamine and noradrenaline (in the presence of both resting and stimulating concentrations of potassium) was also unaffected whereas release of endogenous serotonin was significantly reduced. In the temporal cortex, noradrenergic markers (concentration of noradrenaline and uptake of radiolabelled noradrenaline) were significantly reduced, to at least 47% of mean control values. These deficits are interpreted as reflecting denervation and were present in patients examined only some two years after developing symptoms of dementia. The ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline (a putative index of noradrenaline turnover) was elevated in the temporal cortex, suggesting increased activity of the remaining noradrenergic varicosities. Noradrenergic markers did not correlate with either clinical or histological indices of the severity of the disease which contrasts with presynaptic cholinergic and serotonergic markers.

Adult↗
PubMed1987

Phosphofructokinase activity in the brain in Alzheimer's disease.

The activity of phosphofructokinase, a key regulatory enzyme of glycolysis, was determined in neurosurgical samples of neocortex obtained from 6 patients with primary degenerative dementia, including 4 with Alzheimer's disease. No consistent reductions were seen compared with samples from nondemented controls. These results contrast with the greatly reduced activity reported previously for postmortem brain specimens from patients with Alzheimer's disease.

Adult↗
PubMed1987

Somatostatin content and release measured in cerebral biopsies from demented patients.

Somatostatin-like immunoreactivity (SLIR) has been assayed in frontal and temporal cortex obtained at diagnostic craniotomy and post-mortem from patients with histologically verified Alzheimer's disease. SLIR content was not significantly different from controls in the frontal and temporal lobes, except in the temporal cortex post-mortem. The K+-stimulated release of endogenous SLIR from tissue prisms ('mini-slices') prepared from neocortex obtained at diagnostic craniotomy from Alzheimer patients was not below the control values. Indices of cholinergic varicosities in similar samples from the frontal and temporal lobes are reduced; accordingly, somatostatin does not seem to be as prominently involved in these regions. Patients with Alzheimer's disease underwent neuropsychological assessment shortly before sampling the temporal lobe. Scores for WAIS full scale and the verbal subscale and the Token Test (measure of language comprehension) significantly correlated with the SLIR content; mean values (fmole/mg protein) were 817, 1468 and 1363 for aphasic and non-aphasic Alzheimer patients and controls, respectively. Ventricular fluid obtained from Alzheimer patients during surgery, did not have a significantly different SLIR content compared to controls. SLIR contents of ventricular fluid and neocortex from demented patients, without any specific histological changes in the sample obtained at diagnostic craniotomy, were also not significantly different from controls. Previously, we have shown that these demented patients, as well as those with histologically verified Alzheimer's disease, have a reduced SLIR content of lumbar fluid so it seems that somatostatin neurones located outside the frontal and temporal lobes are affected relatively early in the disease process.

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