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D G Flood

Publications and source records attributed to D G Flood.

At least 19 recordsLinked to original sources
PubMed1995

[Differential neuronal loss in the hippocampus in normal aging and in patients with Alzheimer disease].

The causal relationship between the neurodegenerative changes that accompany normal ageing and those that characterize Alzheimer's disease is unclear. The high incidence of Alzheimer's disease associated with old age and the presence of its neuropathological signs in non-demented older individuals suggest that these two phenomena involve the same neurodegenerative processes and mechanisms and that Alzheimer's disease is an extension of normal ageing. On the other hand, the identification of environmental and genetic risk factors associated with Alzheimer's disease suggests the involvement of a specific disease process that is not related to normal ageing. The resolution of this fundamental issue is of importance in the design of investigative and therapeutic strategies. In this report, we describe differences in the regional patterns of neuronal loss, in the hippocampal region of the brains of Alzheimer's patients and normal ageing subjects, that indicate that Alzheimer's disease is not the manifestation of accelerated ageing, but the expression of a distinct pathological process.

Aged↗
PubMed1994

Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease.

The distinction between the neurodegenerative changes that accompany normal ageing and those that characterise Alzheimer's disease is not clear. The resolution of this issue has important implications for the design of therapeutic and investigative strategies. To this end we have used modern stereological techniques to compare the regional pattern of neuronal cell loss in the hippocampus related to normal ageing to that associated with Alzheimer's disease. The loss related to normal ageing was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions of 45 normal ageing subjects who ranged in age from 13 to 101 years. The Alzheimer's disease related losses were evaluated from similar data obtained from 7 cases of Alzheimer's disease and 14 age matched controls. Qualitative differences were observed in the regional patterns of neuronal loss related to normal ageing and Alzheimer's disease. The most distinctive Alzheimer's disease related neuron loss was seen in the CA1 region of the hippocampus. In the normal ageing group there was almost no neuron loss in this region (final neuron count in the CA1 region: 4.40 x 10(6) neurons for the Alzheimer's disease group vs 14.08 x 10(6) neurons in the normal ageing group). It is concluded that the neurodegenerative processes associated with normal ageing and with Alzheimer's disease are qualitatively different and that Alzheimer's disease is not accelerated by ageing but is a distinct pathological process.

Adolescent↗
PubMed1994

Increased levels of hemoglobin-derived and other peptides in Alzheimer's disease cerebellum.

Several studies point to the importance of peptides and proteolysis in Alzheimer's disease (AD). Because of its ability to study small proteins and peptides, reverse-phase HPLC was employed to study these species in AD. Cerebellum was chosen for these initial studies because it does not show significant neuronal loss but does show some pathology in AD. Examination of over 600 peptide peaks per case revealed 15 that were elevated in AD. Nine were fragments of hemoglobin, and the remainder included two species of calmodulin, two of myelin basic protein, and one each of 67 kDa neurofilament protein and PEP-19. The cleavage sites on hemoglobin were after hydrophobic residues and immunolocalization was seen preferentially around blood vessel walls and granule cells. The elevation of the non-serum-derived peptides was characteristic of general metabolic changes that occurred in AD cerebellum, and the presence of elevated hemoglobin polypeptides indicated either possible disruption of the blood-brain barrier or selective evasion of it by peptidaceous products. Further studies are required to establish whether hemoglobin fragments have a role in neurodegenerative processes such as AD.

Aged↗
PubMed1991

Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. I. CA1 of hippocampus.

Pyramidal neurons in two subdivisions of CA1 (CA1c and CA1a + b) of hippocampus from human brains obtained at autopsy were studied in Golgi Cox-stained tissue. Seventeen cases were a part of a normal aging series, ranging in age from 43 to 95 years; and 5 cases had Alzheimer's disease (AD). Dendritic extent of apical and basal trees was found to be stable in normal aging. In AD there was a significant loss of total dendritic length and/or average segment length for the apical and basal trees of both subdivisions of CA1. This finding is consistent with the findings of severe pathology in CA1 reported by others. The reductions in overall dendritic extent in CA1a + b in AD could be attributed largely to alterations in the lengths of the terminal segments. Apical and basal trees of CA1c were more severely affected by AD than those of CA1a + b and showed more widespread reductions in numbers of segments as well as lengths of segments.

Adult↗
PubMed1991

Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. II. Subiculum.

The dendritic trees of pyramidal neurons of layer III or the external pyramidal layer of the subiculum have been studied in Golgi Cox-stained human tissue obtained at autopsy. Fifteen cases were neurologically and psychiatrically normal and ranged in age from 43 to 95 years; and 5 cases had clinically and neuropathologically defined Alzheimer's disease (AD). Measures of dendritic extent did not change in normal aging in either the apical or basal trees. In AD there was a significant reduction in dendritic extent of the apical trees and a non-significant reduction in extent of the basal trees. These alterations of the dendritic trees in AD are consistent with the findings of severe pathology in the subiculum reported by others. Changes in AD were mainly a reduction in numbers of segments, rather than in the lengths of segments.

Adult↗
PubMed1990

Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease.

Different patterns of age-related dendritic change have been reported in different zones of the human hippocampal region in the normal and Alzheimer's disease (AD) brain. In normal aging there is an increase in average (net) dendritic extent (which we interpret as plasticity) in the parahippocampal gyrus and dentate gyrus. There is net stability of dendritic extent in CA2-3, CA1, and subiculum. In regions that show plasticity in normal aging, dendrites in AD show reduced or aberrant plasticity. In regions that show stability in normal aging, dendrites either are stable or regress in AD, depending upon how severely involved the region is with the pathology of AD.

Aged↗
PubMed1988

Estimating the number of granule cells in the dentate gyrus with the disector.

A practical example is given of how a newly developed stereological estimator of particle number, the disector, can be used to make estimates of neuron number in the dentate gyrus of rats. The estimates are free of biases related to lost caps, overprojection and assumptions about size, shape and orientation of the objects that are counted. The disector principle and the practical considerations relating to histological preparations and sampling are presented.

Animals↗
PubMed1987

Volumes of the components of the hippocampus in the aging F344 rat.

Much of the recent data on cells, synapses, and other structures in the dentate gyrus and hippocampus as a function of age are packing density or volume fraction data. In order to estimate total numbers, volumes, or surface areas of cells, synapses, vessels, etc., as a function of age, the total volumes of the subregions of the dentate gyrus and hippocampus must be known. The volumes of these subregions, visualized with the Timm stain, have been determined in 24 F344 rats from 4 to 37 months of age. Volumes of the various structures showed age-related increases which were statistically significant for the perforant path zone of the dentate gyrus molecular layer, as well as the total molecular layer, the hilus, and regio inferior and total mossy fiber systems. If the 4-month age group is eliminated from consideration, only the ratio of the volume of the mossy fiber zones to the volume of the perforant path zones of the dentate molecular layer increases significantly with age. Our general finding of lack of volumetric reorganization of the subdivisions of the hippocampal region between 12 and 37 months suggests that studies of the packing densities of structures in most of these zones may be considered comparable across ages, assuming comparability of sampling regions.

Aging↗
PubMed1987

Dendritic extent in human CA2-3 hippocampal pyramidal neurons in normal aging and senile dementia.

The extent of dendritic trees of pyramidal neurons of the CA2-3 field of the hippocampus of 20 human brains obtained at autopsy was quantified in Golgi Cox-stained tissue. Fifteen cases were neurologically and psychiatrically normal and ranged in age from 43 to 95 years. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of both the apical and basal trees of CA2-3 pyramidal neurons was found to be unchanged from middle age to very old age. This finding of net stability of dendritic extent is in contrast to previous quantitative reports of either continued dendritic growth in human parahippocampal gyrus or of dendritic growth followed by regression in human dentate gyrus. This finding is consistent with the suggestion that changes in dendritic extent in normal aging are a function of the balance between regressive and proliferative influences and are region specific. In cases with SD, dendritic extent of both the apical and basal trees was found to be similar to that of the normal age-matched cases. These data are consistent with those of others suggesting relative sparing of the CA2-3 field from the degenerative changes in senile dementia.

Adult↗
PubMed1987

Dendritic extent in human dentate gyrus granule cells in normal aging and senile dementia.

Granule cells of the hippocampal dentate gyrus of 22 human brains obtained at autopsy were studied in Golgi-Cox stained tissue. Seventeen cases were cognitively normal and ranged from 43 to 95 years of age. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of granule cells was found to increase in normal aging between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of normal aging human brain and suggests that changes in dendritic extent in normal aging are region and age specific. In cases with SD, dendritic extent was greatly reduced when compared with the normal cases of the same age (seventies) and slightly reduced when compared with middle-aged cases. The very old normal and SD cases were similar in dendritic extent, suggesting that the functional and memory deficits characteristic of SD cannot be explained solely on the basis of the static status of dendritic extent of single neurons.

Aged↗
PubMed1986

Failed compensatory dendritic growth as a pathophysiological process in Alzheimer's disease.

In normal human aging the remaining neurons of two areas of the hippocampal region have been found to compensate for age-related neuronal loss by proliferating new dendrites. In Alzheimer's disease (AD) the layer II pyramidal neurons of the parahippocampal gyrus fail to show this compensatory response, in spite of a probable, exaggerated disease-related loss of neurons. In AD the dentate gyrus granule cells of the hippocampus also show a reduced amount of the compensatory response. This failure of the AD brain to show the normal compensatory plastic response, seen in normal aging as dendritic growth, may be viewed as one of the pathophysiological processes of the disease.

Aged↗
PubMed1985

Age-related dendritic growth in dentate gyrus of human brain is followed by regression in the 'oldest old'.

Dendritic extent in dentate gyrus granule cells of normal aging human brain was found to increase between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of aging human brain. This new result reinforces the concept of age and region specificity in changes in dendritic extent.

Adult↗
PubMed1985

Stability of numbers but not size of mouse forebrain cholinergic neurons to 53 months.

In normal mammalian aging there is a reduction of cholinergic markers in a variety of regions. To determine whether this reduction is related to reduced numbers of basal forebrain cholinergic neurons, we counted the number and measured the sizes of the magnocellular acetylcholinesterase-positive neurons in this region of 7, 15, and 53-month-old C57Bl/6NNIA mice. Data were collected from coded slides containing the medial septum, nucleus of the diagonal band, magnocellular preoptic nucleus, and nucleus basalis magnocellularis. There was no decline in numbers of basal forebrain acetylcholinesterase-positive neurons in any of the regions studied. However, cell sizes showed a progressive age-related decline which was greatest in the nucleus basalis magnocellularis.

Acetylcholinesterase↗
PubMed1985

A Golgi study of hypothalamic transplants in young and old host rats.

The supraoptic nucleus of the F344 rat shows an age-related dendritic regression. In order to determine whether this previously observed dendritic regression may have been related to extrinsic (to the cell) hormonal, neurotoxic, or other circulating factors unique to the hypothalamus of older brains, we conducted a quantitative Golgi study of F344 embryonic anterior hypothalamic transplants into the third ventricle of young adult (5 months) and older (25 months) male F344 rats. Three months following transplantation there were no qualitative effects of host age on neuronal morphology, nor were there quantitative effects on transplant size, dendritic length or branching frequency within the transplanted tissue. These results suggest that either (a) there were no age-related changes in factors in the host brain which were sufficient to significantly affect dendritic extent or, (b) intrinsic connections or other properties within the transplant may be important in moderating the effect of the milieu of the aged brain on the transplanted tissue.

Aging↗
PubMed1985

Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione.

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD), which produces transport abnormalities and swellings in the large diameter fibers of the peripheral nervous system, was administered to cats in an attempt to produce similar selective effects in the optic tract. Anatomical findings indicate damage to one type of retinal ganglion cell, the large (alpha) or Y-cell class, both during dosing and after a long recovery period. This selective involvement of the large ganglion cells during dosing was shown by decreased retrograde transport of HRP in these cells relative to smaller cells. Such selectivity was not apparent in axonal swellings and neurofilament accumulations which were present in fibers of all diameters in the distal optic tract. Visual threshold studies during dosing showed a loss of flicker resolution with preservation of visual acuity, a result consistent with the different physiological properties of alpha and beta ganglion cells. In one cat, which survived dosing for a period of 8 months, there was a dramatic reduction in the number of large cells and a pronounced shrinkage of those that remained, but no observed changes in other cell types. Thus, this intoxication caused (1) axonal swellings which were not selective for fiber size; (2) a selective defect in axonal transport with later neuronal degeneration and shrinkage that were limited to large cells; and (3) a loss of flicker resolution that may reflect dysfunction of large ganglion cells.

Animals↗