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G Blessed

Publications and source records attributed to G Blessed.

At least 55 records · Page 3Linked to original sources
PubMed1981

Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease.

Abnormalities of the noradrenergic system in Alzheimer's disease have been investigated by comparing quantitative histological and biochemical components of this transmitter system (locus coeruleus neuron counts and cortical dopamine beta-hydroxylase (DBH) activity, respectively) in a series of demented and non-demented cases. Cortical activities of the noradrenergic enzyme, DBH, did not correlate significantly with the number of locus coeruleus neurons, a finding which contrasts with the previous observations in animal brains of reductions in cortical DBH following locus coeruleus lesions. The extent of Alzheimer-type abnormalities, assessed from either morphological measures (mean plaque counts) or clinical measures (Mental Test Scores) of severity, was not significantly related to the cortical activity of DBH in the present series of cases, although non-significant trends were apparent. In contrast the activity of the cholinergic enzyme choline acetyltransferase did, as previously reported, correlate significantly with the extent of Alzheimer-type abnormalities, suggesting that abnormalities of the cholinergic system are more closely associated with specific aspects of the Alzheimer disease process than those of the noradrenergic system.

Alzheimer Disease↗
PubMed1981

Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex.

Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay.

Alzheimer Disease↗
PubMed1981

Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes.

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.

Aged↗
PubMed1980

Coenzyme A-acetylating enzymes in Alzheimer's disease: possible cholinergic 'compartment' of pyruvate dehydrogenase.

In the mammalian central cholinergic system the precise mechanism for the production of acetyl-CoA used in acetylcholine synthesis has not yet been identified. As a possible means of investigating this problem the relationship between the activities of several enzymes which can synthesize acetyl-CoA and the cholinergic defect of Alzheimer's disease has been examined. Small, but significant reductions in the activities of pyruvate dehydrogenase, ATP-citrate lyase and acetoacetyl-CoA thiolase were found in post mortem brain tissue from cases of Alzheimer's disease, and the decrease in pyruvate dehydrogenase appeared to be related to the extent of the cholinergic defect (as indicated by loss of choline acetyltransferase). Furthermore, the regional distribution of choline acetyltransferase was similar to that of pyruvate dehydrogenase but not to the distribution of the other enzymes investigated in normal human brain tissue. These observations tend to support a recent suggestion that there may be a particular form of pyruvate dehydrogenase associated with cholinergic neurones.

ATP Citrate (pro-S)-Lyase↗
PubMed1980

Histochemical observations on cholinesterase activities in the brains of elderly normal and demented (Alzheimer-type) patients.

The extent and distribution of acetylcholinesterase staining in the hippocampus has been compared in normal elderly cases and patients with Alzheimer's disease. In both groups some senile plaques and neurofibrillary tangles stain positively with acetylcholinesterase and in Alzheimer's disease there is a reduction in acetylcholinesterase staining of nerve processes. The positive staining of processes in senile plaques suggests that they are, at least partly, derived from cholinergic, axonal fibres and the decrease in acetylcholinesterase staining of nerve processes may indicate a diminution in cholinergic, afferent input fibres to the hippocampus in Alzheimer's disease.

Acetylcholinesterase↗
PubMed1980

Hippocampal free amino acids in Alzheimer's disease.

The free amino acid content of the hippocampus, obtained at postmortem, has been analysed in cases of Alzheimer's disease and compared with normal cases. There were no significant differences in the levels of 23 amino acids including the transmitter candidates gamma-aminobutyric, glutamic or aspartic acids. This finding is interpreted in relation to present knowledge of transmitter pathways in the region of the hippocampus. A tendency for some amino acids to be increased in the Alzheimer group reached statistical significance for arginine. This observation is consistent with increased proteolytic or peptidase activity in Alzheimer's disease.

Aged↗
PubMed1978

Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.

Necropsy brain tissue from normal (control) patients and patients with depression and dementia was examined for activities of various cholinergic components, and these related to the degree of senile plaque formation and extent of intellectual impairment. Choline acetyltransferase and acetylcholinesterase activities decreased significantly as the mean plaque count rose, and in depressed and demented subjects the reduction in choline acetyltransferase activity correlated with the extent of intellectual impairment as measured by a memory information test; muscarinic cholinergic receptor binding activity remained unchanged with increasing senile plaque formation but butyrylcholinesterase activity increased. The results suggest a close relation between changes in the cholinergic system and Alzheimer's dementia, but the precise role of the system in this disease remains to be elucidated.

Acetylcholinesterase↗
PubMed1977

Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue.

Reductions in 2 neurotransmitter synthesizing enzymes in brain, glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT), have been found in dementias of different origins, including senile dementia (Alzheimer type). Significant reductions in cerebral GAD have also been found in depression (unipolar). The GAD reductions did not generally appear to be localised in any specific region of the brain examined. However, the reduction of CAT in the hippocampus, relative to reductions in other areas examined, was substantially greater in the brains with Alzheimer-type changes. GAD and CAT activities in normal brains were examined for the effects of some variable factors inherent in necropsy biochemical measurements. These factors included: (i) age; (ii) agonal status; (iii) time of death, and (iv) delay in tissue sampling; and GAD was found to be significantly influenced by (ii), (iii) and (iv) and CAT by (i), (iii) and (iv). None of these factors accounted for the total alterations in the enzyme activities of the mentally abnormal brains. The results indicate that reductions in cerebral GAD require to be interpreted with caution in view of the sensitivity of this enzyme to premortem status but that reductions in cerebral CAT may be a more reliable index of pathological change in senile (Alzheimer-type) dementia.

Age Factors↗