Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-02T18:44:32.902Z Has data issue: false hasContentIssue false

Alzheimer's Disease and Chromosome 14

Different Gene, Same Process?

Published online by Cambridge University Press:  02 January 2018

Paul Harrison*
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX

Extract

Over the past three years, progress in the molecular genetics of familial Alzheimer's disease has been fast and fundamental. The seminal finding that some cases are due to a mutation in the β-amyloid precursor protein (APP) gene has been followed by the discovery of a major additional locus for the disease on chromosome 14. The combined data suggest that the genetic sites accounting for most early-onset familial Alzheimer's disease cases have now been located. In addition, research is revealing the mechanisms by which the genes exert their pathogenicity. This promises to provide the explanatory link between the genes and the clinicopathological syndrome. The ultimate goal, an understanding in similar terms of the much commoner senile, sporadic form of Alzheimer's disease, is now a realistic target.

Type
Annotation
Copyright
Copyright © The Royal College of Psychiatrists 

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

Alzheimer's Disease Research Group (1991) Molecular classification of Alzheimer's disease. Lancet, 337, 13421343.Google Scholar
Chartier Harlin, M. C., Crawford, F., Houlden, H., et al (1991) Early onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature, 353, 844846.Google Scholar
Citron, M., Oltersdorf, T., Haass, C., et al (1992) Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature, 360, 672674.Google Scholar
Gandy, S. & Greengard, P. (1992) Amyloidogenesis in Alzheimer's disease: some possible therapeutic opportunities. Trends in Pharmacological Sciences, 13, 108113.Google Scholar
Goate, A., Chartier Harlin, M. C., Mullan, M., et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349, 704706.CrossRefGoogle ScholarPubMed
Hardy, J. A. (1992) An ‘anatomical cascade’ hypothesis for Alzheimer's disease. Trends in Neuroscience, 15, 200201.Google Scholar
Hardy, J. A. & Allsop, D. (1991) Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends in Pharmacological Sciences, 12, 383388.Google Scholar
Hardy, J. A. & Mullan, M. (1992) Alzheimer's disease: in search of the soluble. Nature, 359, 268269.Google Scholar
Harrison, P. J. & Mullan, M. (1991) Alzheimer's disease: the significance of a β-amyloid precursor protein gene mutation. Current Opinion in Neurology and Neurosurgery, 4, 908913.Google Scholar
Harrison, P. J. & Roberts, G. W. (1991) ‘Life, Jim, but not as we know it.’ Transmissible dementias and the prion protein. British Journal of Psychiatry, 158, 457470.Google Scholar
Harrison, P. J., Procter, A. W., Exworthy, T., et al (1993) Heat shock protein (hsx70) mRNA expression in human brain: effects of neurodegenerative disease and agonal state. Neuropathology and Applied Neurobiology, 19, 1021.Google Scholar
Hendriks, L., van Duijn, C. M., Cras, P., et al (1992) Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene. Nature Genetics, 1, 218221.Google Scholar
Joachim, C. L. & Selkoe, D. J. (1992) The seminal role of β-amyloid in the pathogenesis of Alzheimer's disease. Alzheimer's Disease and Associated Disorders, 6, 734.Google Scholar
Mayer, R. J., Landon, M., Laszlo, L., et al (1992) Protein processing in lysosomes: the new therapeutic target in neurodegenerative disease. Lancet, 340, 156159.Google Scholar
Medori, R., Tritschler, H.-J., Leblanc, A., et al (1992) Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. New England Journal of Medicine, 326, 444449.Google Scholar
Mullan, M. (1992) Familial Alzheimer's disease: second gene locus located. British Medical Journal, 305, 11081109.Google Scholar
Mullan, M., Crawford, F., Axelman, K., et al (1992a) A pathogenic mutation for probable Alzheimer's disease in the amyloid precursor protein gene at the N terminus of β-amyloid. Nature Genetics, 1, 245247.CrossRefGoogle Scholar
Mullan, M., Houlden, H., Windelspecht, M., et al (1992b) A locus for familial early onset Alzheimer's disease on the long arm of chromosome 14, proximal to α1-antichymotrypsin. Nature Genetics, 2, 245247.CrossRefGoogle Scholar
Murphy, M. (1992) The molecular pathogenesis of Alzheimer's disease: clinical prospects. Lancet, 340, 15121515.Google Scholar
Murrell, J., Farlow, M., Ghetti, B., et al (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science, 254, 9799.Google Scholar
Pericak-Vance, M. A., Bebout, J. L., Gaskell, P. C., et al (1991) Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. American Journal of Human Genetics, 48, 10341050.Google Scholar
Royston, M. C., Rothwell, N. & Roberts, G. W. (1992) Alzheimer's disease: from pathology to potential treatments. Trends in Pharmacological Sciences, 13, 131133.Google Scholar
St George Hyslop, P. H., Haines, J. L., Farrer, L. A., et al (1990) Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature, 347, 194197.Google Scholar
Schellenberg, G., Bird, T., Wijsman, E., et al (1992) Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science, 258, 668671.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.