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D M Mann

Publications and source records attributed to D M Mann.

At least 91 records · Page 5Linked to original sources
PubMed1994

beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects.

Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.

Aged↗
PubMed1993

Frontal lobe dementia is not a variant of prion disease.

Frontal lobe dementia (FLD) is a syndromal diagnosis with a variable pathology. It has been argued that FLD is a dementing disorder which should be nosologically and etiologically distinguished from other types of dementia. However, similarities with prior disease and Alzheimer's disease have led to the suggestion that FLD is a variant of one or other of these dementias. We have tested this line of argument by examining the frontal cortex and cerebellum of 14 FLD cases and probing the molecular pathology using well characterized antibodies to prion protein and beta-amyloid protein. No prion protein deposits or significant levels of beta-amyloid protein were detected. FLD is a dementing disorder whose molecular pathology, whilst as yet uncharacterised, can be distinguished from those of other dementing disorders.

Aged↗
PubMed1993

The topographic distribution of brain atrophy in frontal lobe dementia.

The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT + MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT + MND. Grey and white matter were affected equally in DFT alone although in DFT + MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies.

Aged↗
PubMed1993

The topographic distribution of brain atrophy in Huntington's disease and progressive supranuclear palsy.

The topographic distribution of brain atrophy was quantified by image analysis of fixed coronal brain slices from 12 patients dying with Huntington's disease (HD) and from 4 other patients dying with progressive supranuclear palsy (PSP). In HD, atrophy was maximal within the caudate nucleus, putamen and globus pallidus. However, the cerebral cortex was also atrophied with reductions in cross-sectional area within frontal, temporal and parietal lobes. In general, more white matter than grey matter was lost leading to an elevation in the grey/white matter ratio. The amygdala and thalamus were reduced in area. In PSP, lesser reductions in cortical area than those of HD were seen, these again being mostly due to a loss of white matter, resulting in an elevation of the grey/white ratio. The globus pallidus and thalamus were decreased in area, but no changes in the caudate nucleus and putamen were measured.

Adult↗
PubMed1993

Familial progressive aphasia: its relationship to other forms of lobar atrophy.

Two brothers presented with slowly progressive aphasia. One brother, who became behaviourally disturbed only at the end of his illness, was found at necropsy to have predominant left frontotemporal atrophy. The other brother developed severe behavioural disturbances shortly after the onset of language impairment. His brain revealed bilateral frontotemporal atrophy. In both there was non-Alzheimer's disease pathology with the histological features of loss of large cortical nerve cells, spongiform change and mild gliosis. The differential anatomical atrophy supports the view that clinical manifestations of lobar atrophy are dictated by the topographical distribution of a common underlying pathology, linking the syndromes of progressive aphasia to dementia of frontal lobe type (DFT) and DFT with motor neuron disease.

Aphasia↗
PubMed1993

Dementia of frontal lobe type: neuropathology and immunohistochemistry.

Brains from 12 patients dying with a clinical diagnosis of frontal lobe dementia have been examined at post mortem. In pathological terms four groups were encountered. Groups A and B showed severe frontal and temporal lobe atrophy characterised histologically in group A by severe neuronal loss, spongiform change of the superficial laminae, and mild astrocytosis; in group B severe neuronal loss was accompanied by intense gliosis but with little or no spongiform change. Two patients in this latter group also showed inclusions in frontal cortex and hippocampus typical of "Pick bodies"; such patients were considered as having classic "Pick's disease". Group C patients showed severe striatal atrophy with variable cortical (frontal or temporal) involvement, with histological changes similar to patients in groups A and B. The single patient in group D showed mild frontotemporal atrophy with spongiform degeneration of the superficial laminae of the cortex and nigral damage, and was considered to have motor neuron disease with dementia. This study is consistent with previous reports showing that the clinical syndrome of frontal lobe dementia is pathologically heterogeneous. However, the nosological relationships within these pathological variants, and between them and conditions such as progressive aphasia were similar histopathological changes are present, remain uncertain.

Aged↗
PubMed1993

Is the "preamyloid" of diffuse plaques in Alzheimer's disease really nonfibrillar?

Several papers have described an 'amorphous' component of the amyloid in diffuse plaques and it has been suggested that this is 'preamyloid,' which is not organized into fibrils. Because most of the studies have been performed on autopsy tissue it was the purpose of this study to compare the ultrastructure of diffuse amyloid deposits in well preserved Alzheimer's disease biopsy specimens with autopsy tissues from patients with Alzheimer's disease and Down's syndrome. A postembedding immunogold technique with anti-beta/A4 protein demonstrated gold particles exclusively on extracellular amyloid fibrils in both biopsy and autopsy brains. We have presented evidence that suggests the claim for the existence of an amorphous component within the beta/A4 protein-positive material is unconvincing.

Aged↗
PubMed1992

Tau pathology in a case of familial Alzheimer's disease with a valine to glycine mutation at position 717 in the amyloid precursor protein.

The brain tissue from a case of familial Alzheimer's disease (FAD) caused by a missense (valine to glycine) mutation at codon 717 of the amyloid precursor protein (APP) gene has been examined for the presence of abnormally phosphorylated paired helical filament tau (PHF-tau). There was abundant PHF-tau present, which on Western blots, was indistinguishable from the PHF-tau typical of cases of sporadic Alzheimer's disease and that of another FAD mutation (valine to isoleucine), previously (Neurosci. Lett., 137 (1992) 221-224). This result implies that the cytoskeletal pathology in Alzheimer's disease is biochemically linked to abnormal APP processing and amyloid deposition.

Alzheimer Disease↗
PubMed1992

Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene.

The brain of a 61-year-old patient with familial Alzheimer's disease, showing a missense (valine----glycine) mutation at codon 717 of the amyloid precursor gene, has been examined at postmortem. Sections of brain showed pathological features entirely typical of Alzheimer's disease with no unusual characteristics. It seems therefore that this particular mutation is indeed pathogenic and that the altered amyloid precursor protein resulting from expression of this mutation is processed in a way that triggers or promotes the pathological cascade of Alzheimer's disease.

Adult↗
PubMed1992

Progressive language disorder due to lobar atrophy.

Sixteen patients with progressive language disorder have been studied longitudinally. Anomia was a prominent presenting characteristic and mutism ultimately occurred. Patients, however, were clinically heterogeneous. Some exhibited nonfluent, agrammatic features, whereas others demonstrated a fluent aphasia, with profound loss of word meaning. Although language disorder remained the sole symptom in a minority of patients, in others an associative agnosia or personality and behavioral changes, or both, emerged. Findings on computed tomography and single photon emission tomography mirrored the areas of dysfunction suggested by the neuropsychological profiles and demonstrated abnormalities restricted to the left hemisphere or involving bilateral frontotemporal cortices. Brains of 3 patients, with distinctive clinical pictures, have been examined at autopsy. Each revealed a focal distribution of atrophy, gliosis and spongiform change, and an absence of senile plaques and neurofibrillary tangles. There was clinical and pathological overlap with frontal lobe dementia. We argue that progressive language disorder is clinically heterogeneous and forms part of a spectrum of clinical presentations of non-Alzheimer lobar atrophy.

Aged↗
PubMed1992

Disease-specific patterns of locus coeruleus cell loss.

Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells.

Aged↗
PubMed1992

The effect of age and Alzheimer's disease on pyramidal neuron density in the individual fields of the hippocampal formation.

Pyramidal neuron density was determined at autopsy in the brains of 12 neurologically normal patients (age range 6-87 years) and 18 patients with histopathologically confirmed Alzheimer's disease (AD; age range 62-89 years). Paraffin wax sections were cut at the level of the central part of the cornu ammonis and stained with cresyl fast violet. Pyramidal neuron density was determined in the stratum pyramidale of the presubiculum, subiculum, prosubiculum and CA1-4. The width of the stratum pyramidale in these areas was also determined. There was no significant effect of age on pyramidal neuron density in any of the fields of the hippocampal formation. However, there was a significant decrease in pyramidal neuron density in the subiculum (44%), prosubiculum (28%) and CA1 (41%) of AD brains compared to controls. There was no significant effect of AD on pyramidal neuron density in the presubiculum, CA2 and CA3, but in CA4 it increased (23%) significantly. Pyramidal band width decreased significantly with age in the presubiculum but there was no effect of age on any other region of the hippocampal formation investigated. The width of the stratum pyramidale was significantly lower in the presubiculum (19%), subiculum (30%) and CA3 (17%) of AD compared with control brains. These data suggest that a reduction in pyramidal neuron density within the hippocampal formation does not occur in the absence of underlying pathology. In AD, pyramidal neuron loss predominantly occurs from that sector of the hippocampal formation which comprises the subiculum, prosubiculum and CA1.

Adolescent↗
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↗
PubMed1991

Human neuroblastoma cells treated with aluminium express an epitope associated with Alzheimer's disease neurofibrillary tangles.

A number of studies have implicated aluminium as a possible factor in the pathogenesis of Alzheimer's disease (AD). Following an examination of the uptake of aluminium by human neuroblastoma cells in culture, treated with a range of concentrations of aluminium complexed with ethylene-diaminetetra-acetic acid (EDTA), we have now carried out an immunocytochemical study. Using an antibody to phosphorylated tau protein, which reacts specifically with AD neurofibrillary tangles (NFT), we have found that after treatment periods of 16 days to 8 weeks with aluminium-EDTA, the cells show positive staining with this antibody. No such reaction was detected in cells grown in medium alone, nor in aluminium-EDTA-treated cells subjected to the same immunocytochemical procedure but without added primary antibody. Cells grown in medium plus EDTA, which contains a low level of aluminium contamination, showed a slight reaction. Our system may provide a suitable model for studying the early changes which lead to NFT formation.

Aluminum↗
PubMed1991

The topographic distribution of brain atrophy in Alzheimer's disease.

The extent of regional atrophy in ten patients, aged 52-74 years, dying with Alzheimer's disease uncomplicated pathologically by the effects of advanced old age or cerebrovascular disease, was quantified by image analysis of fixed coronal brain slices. Atrophy of the cerebral cortex was globally distributed, although the temporal lobe was most severely affected. Grey and white matter was in general affected equally. Atrophy was also present within the basal ganglia, particularly the caudate nucleus and putamen. Cerebral cortical atrophy is probably due mostly to neurofibrillary degeneration and loss of intrinsic pyramidal cells and their processes (grey matter) and axons (white matter) although loss of ascending subcortical fibres from regions such as nucleus basalis and locus caeruleus will contribute. Atrophy of the basal ganglia may relate to loss of descending cortical projections.

Aged↗