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Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder
Open accessAbstract
ALZHEIMER'S disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of tbe general uniformity of the disease phenotype1,2. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21 (refs 3,4). But two other studies, one of pre-dominantly multiplex kindreds with a late age-of-onset5, the other of a cadre of kindreds with a unique Volga German ethnic origin6, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedi-grees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
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Cites
PREDISPOSING LOCUS FOR ALZHEIMER'S DISEASE ON CHROMOSOME 21
Goate, A., Owen, M., James, L., Mullan, M., Rossor, M., Haynes, A., Farrall, M., Lai, L. C., Roques, P., Williamson, R., et al. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91725-x · Cited by 270
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Cited by
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659
Self-citationCloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051
Self-citationAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
Self-citationGenetic Dissection of Complex Traits
Lander, E. S., & Schork, N. J. (1994) · Science · doi:10.1126/science.8091226 · Cited by 3,413
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Metadata
- Authors
- St George-Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Broeckhoven, C. V., Goate, A., McLachlan, D. R. C., Orr, H., Bruni, A. C., Sorbi, S., Rainero, I., Foncin, J.-F., Pollen, D., Cantu, J.-M., Tupler, R., Voskresenskaya, N., Mayeux, R., Growdon, J., Fried, V. A., Myers, R. H., Nee, L., Backhovens, H., Martin, J.-J., Rossor, M., Owen, M. J., Mullan, M., Percy, M. E., Karlinsky, H., Rich, S., Heston, L., Montesi, M., Mortilla, M., Nacmias, N., Gusella, J. F., & Hardy, J. A.
- Venue
- Nature
- Published
- 1990-09
- Volume
- 347
- Issue
- 6289
- Pages
- 194-197
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1515586143
- Cited by
- 392
- References
- 1
- FWCI
- 49.84
- Type
- journal article
- Language
- en
- Open access
- green
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- St George-Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Broeckhoven, C. V., Goate, A., McLachlan, D. R. C., Orr, H., Bruni, A. C., Sorbi, S., Rainero, I., Foncin, J.-F., Pollen, D., Cantu, J.-M., Tupler, R., Voskresenskaya, N., Mayeux, R., Growdon, J., Fried, V. A., . . . Hardy, J. A. (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature. https://doi.org/10.1038/347194a0
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
