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Biomedical subjects

D M Mann

Publications and source records attributed to D M Mann.

At least 199 records · Page 11Linked to original sources
PubMed1977

Variations in melanin content with age in the human substantia nigra.

Evidence is presented here that the decrease in mean melanin content we have measured in old age is due, not to a general decline in melanin in all cells, but rather to a selective loss of those nerve cells containing greatest amounts of pigment. This cell loss is likely to be caused by the physical affects of pigment accumulation, per se, upon capacity for protein synthesis, as marked by losses of cytoplasmic RNA and nucleolar shrinkage in melanin rich cells.

Adolescent↗
PubMedDate not supplied

Abnormal RNA metabolism in spinal motor neurons in the wobbler mouse.

RNA metabolism was studied in anterior horn neurons in wobbler mice. In the wobbler mice, RNA content was reduced in histologically normal neurons but not consistently reduced in vacuolated neurons, as compared with normal littermates. Nuclear and nucleolar incorporation of [5--3H]uridine was reduced both in vacuolated and in histologically normal neurons of wobbler mice, while cytoplasmic counts were higher in histologically normal neurons of wobbler mice than in vacuolated neurons or the neurons of normal littermates. These findings point to an abnormality of RNA synthesis which precedes the earliest morphological changes seen in nerve cells with the light microscope. Nuclear [5--3H]uridine uptake was reduced both in small and in large neurons, a finding suggesting that the metabolic abnormality is probably not confined to alpha-motoneurons.

Animals↗
PubMedDate not supplied

Changes in nerve cells of the nucleus basalis of Meynert in Alzheimer's disease and their relationship to ageing and to the accumulation of lipofuscin pigment.

The number of nerve cells in the nucleus basalis of Meynert in normally aged persons is reduced by 30% by 90 years of age and cytoplasmic RNA content and nucleolar volume by about 20%. In Alzheimer's disease the changes are greatly exacerbated, with the cell number being depleted by a further 60% and cytoplasmic RNA content and nucleolar volume by an extra 35%. Moreover, younger patients with Alzheimer's disease show a much greater difference from controls of the same age than do older patients; indeed, by 90 years of age the levels of these changes are similar in Alzheimer's disease and in old age alone. Lipofuscin content is increased to a similar extent with age in both Alzheimer's disease and control patients and was associated with loss of cytoplasmic RNA content and nucleolar volume in both groups. It is suggested that mechanisms which result in the accumulation of this pigment during life also lower the capability of cells of the nucleus basalis of Meynert to withstand disease pathogens, leading to a certain degree of change in old age alone and one which in other persons may be compounded by secondary factors giving the extreme degeneration of Alzheimer's disease.

Age Factors↗
PubMedDate not supplied

An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease.

Observations, in Alzheimer's disease, in the pattern of nerve cell damage and loss, the pathology, microchemistry and immunology of senile plaques and neurofibrillary tangles and alterations in blood vessels are drawn together into a hypothesis that attempts to explain the pathogenesis and progression of the disorder. At the heart of this hypothesis lies a defect in blood brain barrier function and/or structure within the cerebral cortex and this defect may be the cause of the cerebral vessel amyloidosis common in many patients with Alzheimer's disease. Age-related alterations in blood brain barrier allow for damage to nerve terminals and limited formation of senile plaques within cerebral cortex; neurofibrillary tangles are formed within cortical and subcortical nerve cells which project to or near damaged vessels/senile plaques. Uptake of "neurotoxin" at affected terminals and retrograde transport to perikarya causes neurofibrillary tangles to be formed; their accumulation leads to perikaryal changes culminating in cell death and loss. Loss of cells in cortically projecting areas of subcortex such as nucleus basalis, locus caeruleus and dorsal raphe, which terminate on cerebral vessels, causes further blood brain barrier dysfunction, new plaque formation and continued cell loss in cortex and subcortex. Once started, such a process could be self-perpetuating and the initial site of damage could lie within the amygdala/hippocampus with putative pathogenic agent accessing the brain via the olfactory pathways.

Age Factors↗
PubMedDate not supplied

Quantitative changes in cerebral cortical microvasculature in ageing and dementia.

Brains were obtained postmortem from 25 mentally normal patients aged 26 to 96 years and from 3 patients with Alzheimer's disease. Although the number of pyramidal nerve cells within frontal and temporal cortex decreased significantly with age, measures of capillary density correlated only weakly with age. Stronger correlations, however, were noted between measures of capillary density and number of pyramidal cells, irrespective of age or disease. Capillary measures did not differ in 6 of the mentally normal patients who showed a few plaques and tangles in their cortex from those of 6 other patients of similar age who did not show such changes. It is concluded that the extent of the capillary network in the cerebral cortex alters to match the number and activity of functioning nerve cells; changes in quantity of capillary occurring with age or Alzheimer's disease may, therefore, secondarily reflect a primary loss of nerve cells and do not form, per se, part of the degenerative process.

Adult↗
PubMedDate not supplied

Neuronal loss in old people: the effects of ageing or disease?

There is abundant evidence to show that the brains of many persons, who do not suffer from overt neurological or psychiatric disease, deteriorate in structure in old age. However, it still remains uncertain as to whether these changes stem from the effects of an ageing process per se or whether the simply reflect the minor pathological results of clinically incipient disorders such as Alzheimer's disease or Parkinson's disease (conditions which become increasingly widespread in later life) or the cerebral manifestations of systemic disease.

Aged↗
PubMedDate not supplied

Is the pattern of nerve cell loss in aging and Alzheimer's disease a real, or only an apparent, selectivity?

The pattern of neuronal loss from the brain in Alzheimer's disease (AD) is selective, not on the basis of neurotransmitter type, metabolic character or trophic dependence, but only in relationship to the anatomical connection of all affected cell types with the association cortex. The "selectivity" of the process of AD seems to lie with local factors within the cerebral cortex whose presence (or absence) links the processes that lead to the deposition of amyloid (A4) protein, to the neuritic response that results in the production and accumulation of abnormal tau proteins and which, ultimately, form the neurofibrillary tangle and bring about the demise of the neurone.

Aging↗
PubMedDate not supplied

Lectin histochemistry of cerebral microvessels in ageing, Alzheimer's disease and Down's syndrome.

A panel of 14 lectins was used to investigate the expression of saccharides by cerebral microvessels (MBV) in ageing, Alzheimer's disease (AD) and Down's syndrome (DS). Broad increases in lectin binding with age may reflect changes in amount and diversity of glycoproteins due to the thickening of the basement membrane (BM) common in older persons. In AD, and in persons over 50 years of age with DS, binding of e-PHA, 1-PHA and PAA was increased beyond that of age alone, as was that of UEA-I and BSA-1B4 in AD, but not in DS. Persons under 50 years of age with DS showed no changes inappropriate to their age. These specific increases in AD and DS may reflect selective disease-related changes in BM and could indicate an impaired blood-brain barrier (bbb) function or integrity. However, because they occur (in DS) after the deposition of amyloid (A4) protein and onset of neurofibrillary degeneration, it is unlikely they induce plaque and tangle formation. Such changes in MBV could stem from the loss of neurones from locus caeruleus, raphe and nucleus basalis (which are thought to innervate MBV and exert control over blood flow and permeability) that occurs in DS after 50 years of age.

Adolescent↗