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is''0l m 5-HT Ante-mortem (m = metabolite) . ". ~ Post-mortem m 0 Noradrenaline ,,-'-'-'-'0-J ,,-'-'-'-'-'-'- m Dopamine ~ . '-'-'-'-'- . " Somatostatin . '1 Plaques Tangles . ". . ". . 'I Synapse loss ChAT " ACh synthesis l"-,. '-'-'-'-'-'-'-'-'-'-'-'-'- ,,-'-'-'-'-'-'-'-'-'-'-'-'-'-'- Neuronal loss ,,- ,,- . ". o 0. 1 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1. 0 Correlation coefficient with dementia rating Figure 2. 1 Various neurotransmitter and neuropathological measures on neocortex obtained either at diagnostic craniotomy (ante-mortem) or post-mortem and re lationship to cognitive impairment (dementia rating). Asterisks identify significant correlations. Negative and positive correlations are not identified in this represen tation of the data. Only the physiologically relevant measure of cholinergic neurones (acetylcholine synthesis) and indices of cortical pyramidal neurone degeneration (neuronal loss, synapse loss and tangles) correlate with severity of dementia. Note the lack of correlation with the structural marker of cholinergic neurones, ChAT activity. Loss of enzyme exceeded that of acetylcholine synthesis (Sims et al. , 1983a), suggesting a compensatory increase in synthesis in the few remaining neurones. Data derived from Palmer (1987) and Terry et al. (1991). emission tomography (PET) and magnetic resonance, may some day pro vide routine insight into differences in brain functioning. Success in developing rapid and reliable diagnostic procedures, perhaps based on changes in body fluid that reflect specific alterations in brain protein metabolism, should ultimately play an important role in the clinical development of new therapeutic agents.
List of contents
1 Molecular biology of Huntington's disease.- 1.1 Introduction.- 1.2 Linkage analysis.- 1.3 Recombination events.- 1.4 Linkage disequilibrium.- 1.5 Genomic imprinting.- 1.6 Predictive testing.- 1.7 Ethical considerations.- 1.8 Uptake of predictive testing.- 1.9 Counselling.- 1.10 Conclusion.- References.- 2 Neuronal pathology in relation to molecular biology and treatment of Alzheimer's disease.- 2.1 Introduction.- 2.2 Neurotransmission.- 2.3 Glutamate, excitotoxicity and ?-amyloid.- 2.4 Drug therapies.- 2.5 Conclusions.- References.- 3 The aetiology of Alzheimer's disease.- 3.1 General introduction.- 3.2 Aluminium.- 3.3 Viruses.- 3.4 DNA repair.- 3.5 Other possible risk factors.- 3.6 Epilogue.- Acknowledgements.- References.- 4 The molecular genetics of Alzheimer's disease.- 4.1 Introduction.- 4.2 Genetic epidemiology.- 4.3 The molecular genetics of Alzheimer's disease.- 4.4 Future studies.- References.- 5 The molecular biology of the transmissible dementias.- 5.1 Introduction.- 5.2 The infectious agent.- 5.3 The PrP gene and its expression.- 5.4 The PrP.- 5.5 Molecular genetics of the human transmissible dementias.- 5.6 Summary and concluding remarks.- References.- 6 The neurochemistry of schizophrenia.- 6.1 Serotonergic function in schizophrenia.- 6.2 Central noradrenergic function in schizophrenia.- 6.3 Dopamine and schizophrenia.- 6.4 Monoamine oxidase and schizophrenia.- 6.5 GABAergic function in schizophrenia.- 6.6 Neuropeptidergic function in schizophrenia.- 6.7 Glutamatergic systems in schizophrenia.- 6.8 Conclusions.- References.- 7 Molecular biology of schizophrenia.- 7.1 Introduction.- 7.2 Linkage studies.- 7.3 Cytogenetic anomalies and schizophrenia.- 7.4 Mutation analysis in schizophrenia.- 7.5 Summary.- References.- 8 Genetics and molecularbiology of manic-depression.- 8.1 Introduction.- 8.2 Clinical diagnosis and identification of the phenotype.- 8.3 Clinical genetics and models of transmission.- 8.4 Models of genetic transmission.- 8.5 Biological theories and possible candidate genes.- 8.6 Gene finding methods: genetic linkage and allelic association.- 8.7 Genetic (allelic) association analysis and its use in the major psychoses.- References.
