Effect of Li+ therapy and site of origin on cerebrospinal fluid beta-amyloid precursor protein derivatives.
Explore the source record for details and available documents.
Alzheimer Disease↗
Biomedical subjects
M T Webster
Publications and source records attributed to M T Webster.
Protease 'Clipsin' extract activity reflects demographic characteristics of human brain.
'Clipsin' and other peptide bond hydrolase activities that appear to be integral membrane proteins, including two implicated in the formation of the histological hallmarks of Alzheimer's disease, were assayed in the frontal and parietal cortex from a large (n = 45) series of postmortem human brains. Tissues were extracted sequentially with detergent-containing and low ionic strength buffers. The final extracts obtained with detergent-high ionic strength buffer were assayed for peptide-bond hydrolase activity using radiolabelled casein and four chromophore-linked peptide substrates. Hydrolysis of N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide and alpha-casein showed evidence of sensitivity to the presence of Alzheimer's disease (n = 22) and some of the seven other demographic features (postmortem delay; mode of death in the case of one substrate) of the brain samples considered. By contrast, activity towards carbobenzoxy(Z)-Leu-Leu-Glu-2-naphthylamide, Z-Val-Lys-Met-4-methyl-coumaryl-7-amide and Z-Val-Lys-Lys-Arg-4-methoxy-2-naphthylamide were independent of all factors. The results are discussed in terms of damage to a sub-population of protease-containing membranes.
Aged↗
The effects of the competitive NMDA receptor antagonist CPP on the high pressure neurological syndrome in a primate model.
Neurophysiological interactions between the competitive N-methyl-D-aspartate (NMDA) preferring receptor antagonist, CPP (3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonate) and the high pressure neurological syndrome (HPNS) have been investigated in the non-human primate Papio anubis. Eight animals were exposed on two occasions to environmental pressures of 81 atmospheres absolute (ATA) in a hyperbaric chamber, using helium and oxygen. One exposure followed pretreatment with CPP (either 5 or 10 mg/kg i.v. plus 5 mg/kg/hr infusion), the other a saline control. Pretreatment with CPP delayed moderate signs of face tremor and myoclonus and abolished severe signs of whole body tremor and seizure activity. By 81 ATA, scores representing severity of HPNS were significantly reduced by CPP to a mean score, reflecting a level of just mild to moderate limb tremoring (P less than 0.001). Changes in the EEG were observed in channels associated with the frontal, parietal and occipital regions of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the 4 conventional wavebands were analysed. The most striking change was the complete prevention by CPP of the 100% increase in the amplitude of alpha waves at 81 ATA in the frontal region (P less than 0.001). It is concluded that NMDA transmission has a major role in the expression of HPNS.
Animals↗
Brain membrane serine protease activity in human cortex compared with rat: implication for Alzheimer's disease.
Cerebral cortex from humans and rats was extracted sequentially with detergent-containing and low-ionic-strength buffers. The resulting pellet was extracted with detergent/high-ionic-strength buffer to yield a soluble enzyme preparation. This was incubated with substrate prepared from rat cerebral cortical membranes containing amyloid precursor protein-like immunoreactivity (APPLIR) of 116 kD approximate apparent molecular mass. The effectiveness of various enzyme preparations to degrade APPLIR was: routine-post-mortem (pm)-delay human samples > rat pup > short-pm-delay human samples >> adult rat. In incubations with human samples only a 100-kD product accumulated. The activity in human brain was inhibited by phenylmethylsulphonylfluoride, insensitive to Ca2+, correlated with pyramidal neurone numbers but not those of astrocytes and was not significantly higher in Alzheimer's disease compared with controls. These data are discussed in terms of other approaches for studying proteolytic activity to explain the deposition of beta-amyloid protein in this disease.
Aged↗
Preliminary neurochemical findings in non-Alzheimer dementia due to lobar atrophy.
Non-Alzheimer's dementia due to lobar atrophy had choline acetyltransferase activities comparable with control rather than Alzheimer's disease values, based on 3 autopsy proven cases on Pick's disease and biopsies from 3 examples of dementia of frontal lobe type. Muscarinic cholinergic receptors were relatively spared only in Alzheimer's disease. Serotonin receptors were markedly reduced (based on Pick cases) whereas measures that reflected presynaptic serotonergic activity were either not affected or increased. Cerebrospinal fluid and brain tissue measurements suggested that inhibitory interneurones and dopamine release were relatively spared. There was no in vitro evidence of hypometabolism.
Atrophy↗