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Biomedical subjects

D M Mann

Publications and source records attributed to D M Mann.

At least 145 records · Page 8Linked to original sources
PubMed1988

The pathological association between Down syndrome and Alzheimer disease.

The neuropathology of Down syndrome (DS) at middle age is compared with that of Alzheimer disease (AD) at that age, through a review of the published literature and from the author's personal observations on brains from a series of patients of different ages with DS. It is noted that the pathological changes of DS at middle age (i.e. the form and distribution of senile plaques and neurofibrillary tangles, the pattern of involvement (atrophy) of neuronal systems) are qualitatively the same as those of AD at that age, though quantitative differences do occur and these may relate to biological or sociological variations inherent to the two parent populations. It is concluded that in pathological terms patients with DS at middle age do indeed have AD. Some ways in which a study of patients with DS can give insight into the nature and development of the pathological changes of AD are put forward and discussed.

Age Factors↗
PubMed1988

Alzheimer's disease: an olfactory connection?

The density and distribution of senile plaques and neurofibrillary tangles were examined in the olfactory bulbs and tracts, amygdala and hippocampus of 28 patients with Alzheimer's disease, 13 with Down's syndrome and 60 non-demented patients of age range 6-84 years. In all three patient groups comparisons of incidence and severity over the three areas showed the amygdala to be the most commonly and most severely affected area by senile plaques, the hippocampus by neurofibrillary tangles, and the olfactory bulbs and tracts to be the least affected by both. These findings are discussed in relationship to the possibility that the olfactory tracts might provide a portal of entry to the brain for any putative pathogenic agent(s) that might be responsible for the induction of senile plaques and/or neurofibrillary tangles.

Adolescent↗
PubMed1988

Alzheimer's disease and Down's syndrome.

The neuropathology of Down's syndrome at middle age is compared with that of Alzheimer's disease at that age, through a review of the published literature and from the author's personal observations. The pathological changes of Down's syndrome at middle age, i.e. the form and distribution of senile plaques and neurofibrillary tangles, and the pattern of involvement (atrophy) of neuronal systems are qualitatively the same as those of Alzheimer's disease at that age. Quantitative differences do occur and these may relate to biological or sociological variations inherent to the two parent populations. It is concluded that, in pathological terms, patients with Down's syndrome at middle age do indeed have Alzheimer's disease. Some ways in which a study of patients with Down's syndrome can give insight into the nature and development of the pathological changes of Alzheimer's disease are put forward and discussed.

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

Glycogen accumulations in the cerebral cortex in Alzheimer's disease.

The fine structure of granular glycogen bodies (GGB) within the grey matter of the temporal cortex of 11 patients with Alzheimer's disease is described. GGB measure up to 50 microns in diameter and consist of densely packed alpha or beta glycogen granules (never both), neither of which are membrane bound. They were noted in axons, both myelinated and unmyelinated (sometimes close to the dystrophic neurites of senile plaques), and also in other processes of indeterminate origin. Their appearance may relate to disturbances of axonal transport resulting from damage to terminals within evolving senile plaques.

Aged↗
PubMed1987

A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease.

A quantitative morphometric analysis was used to estimate neurone and synapse densities in cerebral cortical biopsy tissues from patients with dementia under 65 years of age and pathologically verified as suffering from Alzheimer's disease. Estimates of the numerical density of neurones and synapses were made in layers II-III and V of both frontal and temporal cortex. A greater loss of synapses than that of neurones was found in Alzheimer's disease, amounting to a minimum (uncorrected for atrophy) of 25% in layers II-III and 36% in layer V of the temporal cortex, and 27% in layer V of the frontal cortex. Values of synapse to neurone ratio also demonstrated this greater loss of synapses, there being on average 38% fewer synapses associated with each surviving neurone in layers II-III of the temporal cortex, 30% fewer in layer V, and a deficit of 14% in layer V of the frontal cortex. It is concluded that a major loss of synapses occurred in this group of patients with Alzheimer's disease, probably at an early stage of the disease, and that the loss is likely to form a fundamental part of the pathological process that underlies the cortical damage of this condition.

Aged↗
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.

Aged↗
PubMed1987

Loss of neurones from cortical and subcortical areas in Down's syndrome patients at middle age. Quantitative comparisons with younger Down's patients and patients with Alzheimer's disease.

Brains were examined after autopsy from 12 patients over 53 years of age with Down's syndrome (in whose brains plaques and tangles were numerous in many areas of cortex and subcortex), 3 patients under 53 years of age with Down's syndrome (in whose brains plaques and tangles were minimal or absent), 10 patients, of age range similar to the older Down's group but with Alzheimer's disease and 5 control patients of age range similar to the younger Down's group. The number of plaques and tangles in the hippocampus and their density within the temporal cortex, the thickness of the temporal cortex, the cross-sectional area of the hippocampus and the relative number and mean nucleolar volume of nerve cells in these cortical and in some subcortical areas were estimated and compared in each of the 4 groups. The relative loss of nerve cells and the decrease in mean nucleolar volume were calculated in percentage terms for the older Down's syndrome patients by reference to data from the younger Down's syndrome patients, whereas such losses in Alzheimer's disease were calculated by reference to the younger control patients. While in qualitative terms, all areas of brain found to be damaged in Alzheimer's disease were also damaged in Down's syndrome at middle age, quantitative differences emerged with the reductions in relative nerve cell number and mean nucleolar volume being significantly less in many areas in Down's syndrome. Conversely plaques and tangles were more numerous in the hippocampus in Down's syndrome though in the temporal cortex plaques were less numerous. It seems, therefore, that although the same pathological process is likely to operate in the two conditions, additional biological and mortality differences between Down's syndrome and the general population may account for the observed quantitative variations.

Adult↗
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

Dopaminergic neurotransmitter systems in Alzheimer's disease and in Down's syndrome at middle age.

In 15 patients with Alzheimer's disease and in 10 with Down's syndrome at middle age, there was severe atrophy, neurofibrillary degeneration and loss of pigmented dopaminergic nerve cells from ventral tegmental area (A10) whereas nerve cells in neighbouring substantia nigra (A9) were much less affected in all three respects. It is suggested that these findings may represent different patterns of damage within the two systems in these conditions which may relate to the presence of Alzheimer type changes (senile plaques) within their respective projection fields.

Aged↗
PubMed1986

Loss of nerve cells from locus coeruleus in Alzheimer's disease is topographically arranged.

Serial sectioning of the locus coeruleus (LC) was employed to determine a topographic loss of nerve cells in patients with Alzheimer's disease (AD). Heaviest loss of nerve cells occurred in the central part of the LC which is thought to project to the temporal cortex and hippocampus, whereas least loss of cells occurred in the most rostral and caudal parts, thought to project to frontal and occipital regions of cortex, respectively. Such changes suggest that the primary damage to these nerve cells in AD occurs within their terminal fields and that perikaryal loss follows as a secondary retrograde change.

Aged↗
PubMed1986

The nucleus basalis of Meynert in multi-infarct (vascular) dementia.

The number and nucleolar volume of nerve cells within the nucleus basalis of Meynert were estimated in 10 patients with Alzheimer's disease, 12 with multi-infarct dementia, 9 with a mixed Alzheimer/multi-infarct dementia and in 10 age-matched controls. As reported previously in Alzheimer's disease, both the number and nucleolar volume of surviving cells was reduced, whereas in multi-infarct dementia no significant change in either measure was noted. In patients with Alzheimer's disease/multi-infarct dementia the loss of nerve cells and reduction in nucleolar volume varied greatly in severity from patient to patient according to the relative balance of Alzheimer and vascular type pathological changes present within each patient.

Aged↗
PubMed1986

The topography of cell loss from locus caeruleus in Alzheimer's disease.

A topographical analysis of nerve cell loss from locus caeruleus in Alzheimer's disease has shown that cell loss is confined to the dorsal areas and occurs uniformly throughout the rostrocaudal length of the locus. By contrast there is no significant cell loss from ventral parts of the locus, at any point along its rostrocaudal length. Dorsally located neurones of the locus project to cerebral cortex; ventrally located neurones to non-cortical areas such as basal ganglia, cerebellum and spinal cord. These data suggest that damage to nerve cells of locus caeruleus in Alzheimer's disease relates primarily to pathological events within their terminal fields, with perikaryal loss following as a secondary retrograde change. The senile plaque may represent the actual site of the damage to nerve terminals.

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↗