Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-19T13:19:25.141Z Has data issue: false hasContentIssue false

Acetylcholine and Alzheimer's Disease

Published online by Cambridge University Press:  02 January 2018

E. Perry*
Affiliation:
Department of Neuropathology and MRC Neuroendocrinology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE

Abstract

The hypothesis that cognitive impairment in Alzheimer's disease is related to cholinergic degeneration in the brain is still, a decade after its formulation, subject to critical evaluation. In marked contrast to the monoamine hypotheses of affective disorders or schizophrenia – based primarily on the mechanisms of action of therapeutic drugs, and yet lacking convincing pathological data on the human brain itself – the cholinergic hypothesis of Alzheimer's disease currently rests largely on evidence of neurochemical pathology in affected tissue, but still depends on effective therapy for its ultimate validation. The urgent need for a means of countering cognitive impairment in degenerative dementias such as Alzheimer's disease (probably the most important cause of intellectual decline in old age) hardly needs emphasising. In this annotation, a number of key questions specifically relating to the cholinergic involvement in Alzheimer's disease are considered. These questions are already being answered both within and, as so often in the history of biological psychiatry, outside the immediate area of investigation.

Type
Annotation
Copyright
Copyright © Royal College of Psychiatrists, 1988 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bartus, R. T., Flicker, C., Dean, R. L., Fisher, S., Ponteirovo, M. & Figueredo, J. (1986) Behavioural and biochemical effects of nucleus basalis magnocellularis lesions: implications and possible relevance to understanding and treating Alzheimer's disease. Progress in Brain Research, 70, 345361.CrossRefGoogle ScholarPubMed
Beatty, W. W., Butters, N. & Janowsky, D. S. (1986) Patterns of memory failure after scopolamine treatment: implications for the cholinergic hypothesis of dementia. Behavioural and Neural Biology, 45, 196211.CrossRefGoogle Scholar
Bowen, D. M. & Davison, A. N. (1986) Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. British Medical Bulletin, 42, 7580.CrossRefGoogle ScholarPubMed
Changeux, J.-P., Klarsfield, A. & Heidman, T. (1987) The acetylcholine receptor and molecular models for short and long-term learning In The Neural and Molecular Bases of Learning (eds Changeux, J.-P. and Konishi, M.), pp. 3184. Chichester: John Wiley & Son.Google Scholar
Cross, A. J., Slater, P., Simpson, M., Deakin, J. F. W., Perry, R. H. & Perry, E. K. (1987) (3H) – Asparate binding in cerebral cortex in patients with Alzheimer's and Parkinson's disease. Neuroscience Letters 79, 213217.Google Scholar
Flynn, D. D. & Mash, D. L. (1986) Characterisation of l-(3H) nicotine binding to human cerebral cortex: comparison between Alzheimer's disease and the normal. Journal of Neurochemistry, 47, 19481952.Google Scholar
Gage, F. H. & Bjorklund, A. (1986) Cholinergic septal grafts into the hippocampus formation improve the spatial learning and memory in aged rats by an atropine sensitive mechanism. Journal of Neuroscience, 6, 237247.Google Scholar
Greenberg, M. E., Ziff, E. B. & Greene, L. D. (1986) Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science, 234, 8082.Google Scholar
Ismail, Z., Millar, T. J., Smith, D. B. & Chubb, I. W. (1986) Acetylcholinesterase generates enkephalin-like immunoreactivity when it degrades soluble proteins (Chromogranins) from adrenal chromaffin granules. Brain Research, 376, 230238.CrossRefGoogle Scholar
Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K. & Muller-Hill, B. (1987). The precursor of Alzheimer's disease amyloid A 4 protein resembles a cell surface receptor. Nature, 325, 733737.Google Scholar
Man in't Veld, A. J., Boomsma, F., Moleman, P. & Schalekamp, M. A. D. H. (1987) Congenital dopamine-beta hydroxylase deficiency. The Lancet, i, 183187.Google Scholar
Maragos, W. F., Greenamyre, J. T., Penney, J. B. & Young, A. B. (1987) Glutamate dysfunction in Alzheimer's disease: a hypothesis. Trends in Neuroscience, 10, 6568.CrossRefGoogle Scholar
Perry, E. K. (1986) The cholinergic hypothesis – ten years on. British Medical Bulletin, 42, 6369.Google Scholar
Perry, E. K., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P. H. & Perry, R. H. (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. British Medical Journal, ii, 14571459.CrossRefGoogle Scholar
Perry, E. K., Perry, R. H., Smith, C. J., Purohit, D., Bonham, J., Dick, D. J., Candy, J. M., Edwardson, J. A. & Fairburn, A. (1986) Cholinergic receptors in cognitive disorders. Canadian Journal of Neurological Sciences, 13, 521527.Google Scholar
Rosenberg, M. B., Breakefield, X. O. & Hawrot, E. (1987) Targeting of liposomes to cells bearing NGF receptors mediated by biotinylated NGF. Journal of Neurochemistry, 47, 865875.Google Scholar
Roth, M. (1986) The association of clinical and neurobiological findings and its bearing on the classification and aetiology of Alzheimer's disease. British Medical Bulletin, 42, 4250.CrossRefGoogle Scholar
St George Hyslop, P., Tanzi, E. E., Polinsky, R. J., Haines, J. L., Nee, L., Watkins, P. C., Myers, R. H. & Feldman, R. S. (1987) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science, 235, 885889.Google Scholar
Summers, W. K., Majouski, L. V., Marsh, G. M., Tackiki, K. & Kling, A. (1986) Oral tetrahydro-aminoacridine in long term treatment of senile dementia, Alzheimer type. New England Journal of Medicine, 315, 12411245.Google Scholar
Whitehouse, P. J., Martino, A. M., Antuono, P. G., Lowenstein, P. R., Coyle, J. T., Price, D. L. & Kellar, N. J. (1986) Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Research. 371, 146151.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.