Biomedical subjects

D Neary

Publications and source records attributed to D Neary.

115 records · Page 7Linked to original sources

PubMedDate not supplied

Neurofibrillary pathology and protein synthetic capability in nerve cells in Alzheimer's disease.

Nucleolar volume was measured in nerve cells of the temporal cortex in cases of Alzheimer's disease, obtained at both biopsy and autopsy. Measurements were made on those nerve cells containing neurofibrillary tangles and also on ones free of such changes. Results showed that nucleolar volume is significantly reduced, by at least 40%, in both tangle and non-tangle bearing cells, in both biopsy and autopsy cases, when compared with corresponding values from appropriate control cases. Furthermore, in the autopsy cases, nerve cell nucleolar volume was reduced by a further 30% in tangle bearing cells compared to non-tangle bearing neighbours. No such difference was noted in these cells in the biopsy cases. These findings imply that alterations in protein synthetic capability occur in nerve cells early in the course of Alzheimer's disease, and that this change is not, at least in these initial stages, related to accumulation of neurofibrillary material within the cell body, although later on such accumulation may result in added disruption of cell metabolism.

Adult↗

PubMedDate not supplied

An ultrastructural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer's disease.

Quantitative morphometric (stereological) methods have been used to assess the effects of accumulation of neurofibrillary material on the fine structure of pyramidal cells in biopsy specimens of temporal cortex from nine patients with Alzheimer's disease. When compared with non-tangled cells from the same patients, tangled cells show an increase in total area of cytoplasm due to the accumulation of tangle and a reduction in the area of the nucleus; the area proportion of the cell body occupied by total cytoplasm, therefore, increases whereas that of the nucleus decreases. Within the total cytoplasm, nucleolar and mitochondrial areas are maintained, but that of lipofuscin is increased, though all are increased when expressed as a proportion of the useful cytoplasm alone (i.e. total cytoplasmic area minus area occupied by tangle). Measures of the amount of rough endoplasmic reticulum and ribosomes are decreased overall in tangled cells, though when related to useful cytoplasm alone such measures approach non-tangled cell values. Measures of smooth endoplasmic reticulum are unaltered throughout. When related to the amount of tangle within cells it was found that the most heavily tangled cells retain 28% of useful cytoplasm, 72% of the nuclear area, 50% of the rough endoplasmic reticulum and 27% of ribosomes present within least tangled and non-tangled cells. By contrast, mitochondrial area is maintained and that of lipofuscin increased. The capacity for protein synthesis in tangled cells appears, therefore, to be progressively decreased with accumulation of tangle, whereas that for oxidative metabolism is maintained and lysosomal activity, perhaps, increased. Neurofibrillary tangle formation and accumulation may, therefore, lead to the eventual death of neurons and be the major cause of nerve cell loss in Alzheimer's disease.

Aged↗

PubMedDate not supplied

A quantitative study of the ultrastructure of pyramidal neurons of the cerebral cortex in Alzheimer's disease in relationship to the degree of dementia.

Quantitative morphometric (stereological) methods have been used to measure the number or amount of organelles in pyramidal nerve cells, unaffected by neurofibrillary degeneration, in biopsy specimens of temporal cortex from 11 patients with Alzheimer's disease, and to relate these to the degree of dementia, as measured by psychometric testing. Only areal proportion (AA) and surface area (SA) of rough endoplasmic reticulum were significantly reduced in line with the severity of the degree of dementia. It is suggested that these changes reflect a progressively diminishing requirement for packaging and transport of replacement proteins, particularly in relation to neurotransmitter metabolism in nerve terminals following the loss of synapses which we have shown to occur in these patients.

Aged↗

PubMedDate not supplied

The progression of the pathological changes of Alzheimer's disease in frontal and temporal neocortex examined both at biopsy and at autopsy.

Brains were obtained at autopsy from five patients with Alzheimer's disease, each of whom had undergone diagnostic craniotomy 3-7 years previously. It was possible, therefore, to examine the number (density) and nucleolar volume of pyramidal nerve cells, and the density of senile plaques and neurofibrillary tangles within the cerebral cortex on two occasions during the progression of their illness, and to assess how these measures might have changed during the period between biopsy and death. In all five patients, at biopsy, the density and the nucleolar volume of pyramidal nerve cells was significantly less than controls and, in general, values for both these measures fell significantly further from biopsy to death. By contrast, in none of the five patients did senile plaque density consistently change from biopsy to death; neurofibrillary tangle density either did not change, or indeed sometimes decreased from biopsy to death. These data show that both the clinical and the pathological progression of Alzheimer's disease is marked by a continuing loss of pyramidal cells from frontal and temporal cortex, although the densities of plaques and tangles within the cortex do not, per se, correlate with the stage of the illness. The usefulness of measurement of plaque and tangle densities as pathological criteria by which the clinical and neurochemical deficits of Alzheimer's disease can be compared in different patients is clearly questionable.

Alzheimer Disease↗

PubMedDate not supplied

The clinical pathological correlates of lobar atrophy.

Three clinical syndromes associated with fronto-temporal cerebral atrophy, studied in one centre are discussed: dementia of frontal type (DFT), DFT and motor neurone disease (MND) and progressive aphasia (PA). The pathological findings in DFT (13 brains), DFT and MND (5 brains) and PA (5 brains) permit a number of clinical pathological groupings. The nosological status of fronto-temporal atrophy is discussed with reference to the literature and it is suggested that a common underlying pathology, including Picks disease as strictly defined by the presence of inclusion bodies, underlies the clinical syndromes, each being determined by the anatomical distribution of the pathology.

Aphasia↗

PubMedDate not supplied

Progressive language dysfunction and lobar atrophy.

The patterns of language disorder associated with 'progressive aphasia' due to lobar atrophy were compared with the language dysfunction of patients with dementia of frontal lobe type (DFT). The progressive aphasias were characterised primarily by impairment at the structural levels of language: phonology, grammar and semantics, whereas DFT was associated primarily with spontaneity and loss of generative capability. However, there was overlap in language symptomatology, particularly with progression of disease. The findings lend support to the argument that progressive aphasia and DFT represent different clinical manifestations of a common pathology, and form part of the spectrum of lobar atrophies.

Adult↗

PubMedDate not supplied

The long-term outcome of head injury: implications for service planning.

As most of those experiencing traumatic brain injury tend to be young, disabled survivors will be gradually accruing in each locality as each year passes. How many need continuing care a decade after injury? How many need day care, or need help with finding work, or continuing support for carers? 190 patients who had been admitted to two UK regional neurosurgical units on average some 7 years earlier were followed up. With an average age of 29 years these patients stayed in hospital for an average 33 days. At follow-up 23% were classified as having moderate disability or worse on the Glasgow Outcome Scale, including 7.4% who had died subsequent to discharge. Survivors were given a neuropsychological assessment and a socioeconomic interview. Of the survivors, 17% had failed to make a good recovery, but 36% were failing to occupy their time in a meaningful way. Age over 30 at time of injury, not occupied before injury, and above-average length of stay were some of the predictors for failing to occupy time. Quality of life was severely curtailed for those who could not occupy their time, as was the case for their carers. Appropriate counselling, vocational evaluation and family support in the early years following injury may help to improve quality of life for both the head-injured person and their carers.

Activities of Daily Living↗