Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder - PubMed (original) (raw)
. 1990 Sep 13;347(6289):194-7.
doi: 10.1038/347194a0.
J L Haines, L A Farrer, R Polinsky, C Van Broeckhoven, A Goate, D R McLachlan, H Orr, A C Bruni, S Sorbi, I Rainero, J F Foncin, D Pollen, J M Cantu, R Tupler, N Voskresenskaya, R Mayeux, J Growden, V A Fried, R H Myers, L Nee, H Backhovens, J J Martin, M Rossor, M J Owen, M Mullan, M E Percy, H Karlinsky, S Rich, L Heston, M Montesi, M Mortilla, N Nacmias, J F Gusella, J A Hardy; FAD Collaborative Study Group; et al.
Collaborators, Affiliations
- PMID: 2395471
- DOI: 10.1038/347194a0
Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder
P H St George-Hyslop et al. Nature. 1990.
Abstract
Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, 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 pedigrees 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.
Comment in
- Alzheimer's disease. Dominant susceptibility genes.
Martin GM, Schellenberg GD, Wijsman EM, Bird TD. Martin GM, et al. Nature. 1990 Sep 13;347(6289):124. doi: 10.1038/347124a0. Nature. 1990. PMID: 2395467 No abstract available.
Similar articles
- Genetic analysis of Alzheimer's disease: a summary of contributions to GAW8.
Wijsman EM. Wijsman EM. Genet Epidemiol. 1993;10(6):349-60. doi: 10.1002/gepi.1370100604. Genet Epidemiol. 1993. PMID: 8314026 Review. - [The genetics of Alzheimer's disease].
Pinessi L, Rainero I, Brunetti E, Cerrato P, Cosentino N, Martino C, Vaula G, Bergamini L. Pinessi L, et al. Minerva Psichiatr. 1992 Jul-Sep;33(3):159-64. Minerva Psichiatr. 1992. PMID: 1474878 Italian. - [Linkage analysis in pedigrees with Alzheimer's dementia].
Mazura I, Jirák R, Koukolík F. Mazura I, et al. Vnitr Lek. 1993 Oct;39(10):951-3. Vnitr Lek. 1993. PMID: 8236867 Czech. - The Seattle Alzheimer's disease data set.
Wijsman EM, Bird TD, Martin GM, Schellenberg GD. Wijsman EM, et al. Genet Epidemiol. 1993;10(6):365-9. doi: 10.1002/gepi.1370100606. Genet Epidemiol. 1993. PMID: 8314028 Review. - Linkage analysis of familial Alzheimer disease, using chromosome 21 markers.
Schellenberg GD, Pericak-Vance MA, Wijsman EM, Moore DK, Gaskell PC Jr, Yamaoka LA, Bebout JL, Anderson L, Welsh KA, Clark CM, et al. Schellenberg GD, et al. Am J Hum Genet. 1991 Mar;48(3):563-83. Am J Hum Genet. 1991. PMID: 1998342 Free PMC article.
Cited by
- Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations.
Motazedi E, Cheng W, Thomassen JQ, Frei O, Rongve A, Athanasiu L, Bahrami S, Shadrin A, Ulstein I, Stordal E, Brækhus A, Saltvedt I, Sando SB, O'Connell KS, Hindley G, van der Meer D, Bergh S, Nordestgaard BG, Tybjærg-Hansen A, Bråthen G, Pihlstrøm L, Djurovic S, Frikke-Schmidt R, Fladby T, Aarsland D, Selbæk G, Seibert TM, Dale AM, Fan CC, Andreassen OA. Motazedi E, et al. J Alzheimers Dis. 2022;88(4):1533-1544. doi: 10.3233/JAD-220174. J Alzheimers Dis. 2022. PMID: 35848024 Free PMC article. - Autosomal Dominantly Inherited Alzheimer Disease: Analysis of genetic subgroups by Machine Learning.
Castillo-Barnes D, Su L, Ramírez J, Salas-Gonzalez D, Martinez-Murcia FJ, Illan IA, Segovia F, Ortiz A, Cruchaga C, Farlow MR, Xiong C, Graff-Radford NR, Schofield PR, Masters CL, Salloway S, Jucker M, Mori H, Levin J, Gorriz JM; Dominantly Inherited Alzheimer Network (DIAN). Castillo-Barnes D, et al. Inf Fusion. 2020 Jun;58:153-167. doi: 10.1016/j.inffus.2020.01.001. Epub 2020 Jan 7. Inf Fusion. 2020. PMID: 32284705 Free PMC article. - Analysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP.
Nafikov RA, Nato AQ Jr, Sohi H, Wang B, Brown L, Horimoto AR, Vardarajan BN, Barral SM, Tosto G, Mayeux RP, Thornton TA, Blue E, Wijsman EM. Nafikov RA, et al. Genet Epidemiol. 2018 Sep;42(6):500-515. doi: 10.1002/gepi.22133. Epub 2018 Jun 3. Genet Epidemiol. 2018. PMID: 29862559 Free PMC article. - Cerebrospinal Fluid Biomarkers in Alzheimer's Disease-From Brain Starch to Bench and Bedside.
Pawlowski M, Meuth SG, Duning T. Pawlowski M, et al. Diagnostics (Basel). 2017 Jul 13;7(3):42. doi: 10.3390/diagnostics7030042. Diagnostics (Basel). 2017. PMID: 28703785 Free PMC article. Review. - A review of study designs and statistical methods for genomic epidemiology studies using next generation sequencing.
Wang Q, Lu Q, Zhao H. Wang Q, et al. Front Genet. 2015 Apr 20;6:149. doi: 10.3389/fgene.2015.00149. eCollection 2015. Front Genet. 2015. PMID: 25941534 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical