Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder

P. H. St George-Hyslop, J. L. Haines, L. A. Farrer, R. Polinsky, C. Van Broeckhoven, A. Goate, D. R. Crapper 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. Growdon, V. A. Fried, R. H. MyersL. 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, Koji Abe, L. Amaducci, L. Bergamini, M. Bruyland, S. Cappa, L. Connor, G. De Winter, D. Drachman, R. G. Feldman, M. Fracarro, M. E. Franco, P. Frommelt, S. I. Gavrilova, G. Gei, J. Gheuens, A. Haynes, J. Henry, L. James, M. F. James, B. O'Donnell, S. Piacentini, L. Pinessi, P. Roques, C. Ruiz, J. Swearer, R. E. Tanzi, A. Vandenberghe, M. Vartanian, G. Vaula, P. C. Watkins, R. Williamson

Research output: Contribution to journalArticle

313 Citations (Scopus)

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 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 predominantly 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 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.

Original languageEnglish
Pages (from-to)194-197
Number of pages4
JournalNature
Volume347
Issue number6289
Publication statusPublished - Sep 13 1990
Externally publishedYes

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Chromosomes, Human, Pair 21
Genetic Linkage
Alzheimer Disease
Pedigree
Confounding Factors (Epidemiology)
Diagnostic Errors
Genetic Markers
Neurodegenerative Diseases

ASJC Scopus subject areas

  • General

Cite this

St George-Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Van Broeckhoven, C., Goate, A., ... Williamson, R. (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature, 347(6289), 194-197.

Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. / St George-Hyslop, P. H.; Haines, J. L.; Farrer, L. A.; Polinsky, R.; Van Broeckhoven, C.; Goate, A.; Crapper McLachlan, D. R.; 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.; Abe, Koji; Amaducci, L.; Bergamini, L.; Bruyland, M.; Cappa, S.; Connor, L.; De Winter, G.; Drachman, D.; Feldman, R. G.; Fracarro, M.; Franco, M. E.; Frommelt, P.; Gavrilova, S. I.; Gei, G.; Gheuens, J.; Haynes, A.; Henry, J.; James, L.; James, M. F.; O'Donnell, B.; Piacentini, S.; Pinessi, L.; Roques, P.; Ruiz, C.; Swearer, J.; Tanzi, R. E.; Vandenberghe, A.; Vartanian, M.; Vaula, G.; Watkins, P. C.; Williamson, R.

In: Nature, Vol. 347, No. 6289, 13.09.1990, p. 194-197.

Research output: Contribution to journalArticle

St George-Hyslop, PH, Haines, JL, Farrer, LA, Polinsky, R, Van Broeckhoven, C, Goate, A, Crapper McLachlan, DR, Orr, H, Bruni, AC, Sorbi, S, Rainero, I, Foncin, JF, Pollen, D, Cantu, JM, Tupler, R, Voskresenskaya, N, Mayeux, R, Growdon, J, Fried, VA, Myers, RH, Nee, L, Backhovens, H, Martin, JJ, Rossor, M, Owen, MJ, Mullan, M, Percy, ME, Karlinsky, H, Rich, S, Heston, L, Montesi, M, Mortilla, M, Nacmias, N, Gusella, JF, Hardy, JA, Abe, K, Amaducci, L, Bergamini, L, Bruyland, M, Cappa, S, Connor, L, De Winter, G, Drachman, D, Feldman, RG, Fracarro, M, Franco, ME, Frommelt, P, Gavrilova, SI, Gei, G, Gheuens, J, Haynes, A, Henry, J, James, L, James, MF, O'Donnell, B, Piacentini, S, Pinessi, L, Roques, P, Ruiz, C, Swearer, J, Tanzi, RE, Vandenberghe, A, Vartanian, M, Vaula, G, Watkins, PC & Williamson, R 1990, 'Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder', Nature, vol. 347, no. 6289, pp. 194-197.
St George-Hyslop PH, Haines JL, Farrer LA, Polinsky R, Van Broeckhoven C, Goate A et al. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature. 1990 Sep 13;347(6289):194-197.
St George-Hyslop, P. H. ; Haines, J. L. ; Farrer, L. A. ; Polinsky, R. ; Van Broeckhoven, C. ; Goate, A. ; Crapper McLachlan, D. R. ; 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. ; Abe, Koji ; Amaducci, L. ; Bergamini, L. ; Bruyland, M. ; Cappa, S. ; Connor, L. ; De Winter, G. ; Drachman, D. ; Feldman, R. G. ; Fracarro, M. ; Franco, M. E. ; Frommelt, P. ; Gavrilova, S. I. ; Gei, G. ; Gheuens, J. ; Haynes, A. ; Henry, J. ; James, L. ; James, M. F. ; O'Donnell, B. ; Piacentini, S. ; Pinessi, L. ; Roques, P. ; Ruiz, C. ; Swearer, J. ; Tanzi, R. E. ; Vandenberghe, A. ; Vartanian, M. ; Vaula, G. ; Watkins, P. C. ; Williamson, R. / Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. In: Nature. 1990 ; Vol. 347, No. 6289. pp. 194-197.
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title = "Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder",
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 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 predominantly 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 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.",
author = "{St George-Hyslop}, {P. H.} and Haines, {J. L.} and Farrer, {L. A.} and R. Polinsky and {Van Broeckhoven}, C. and A. Goate and {Crapper McLachlan}, {D. R.} and H. Orr and Bruni, {A. C.} and S. Sorbi and I. Rainero and Foncin, {J. F.} and D. Pollen and Cantu, {J. M.} and R. Tupler and N. Voskresenskaya and R. Mayeux and J. Growdon and Fried, {V. A.} and Myers, {R. H.} and L. Nee and H. Backhovens and Martin, {J. J.} and M. Rossor and Owen, {M. J.} and M. Mullan and Percy, {M. E.} and H. Karlinsky and S. Rich and L. Heston and M. Montesi and M. Mortilla and N. Nacmias and Gusella, {J. F.} and Hardy, {J. A.} and Koji Abe and L. Amaducci and L. Bergamini and M. Bruyland and S. Cappa and L. Connor and {De Winter}, G. and D. Drachman and Feldman, {R. G.} and M. Fracarro and Franco, {M. E.} and P. Frommelt and Gavrilova, {S. I.} and G. Gei and J. Gheuens and A. Haynes and J. Henry and L. James and James, {M. F.} and B. O'Donnell and S. Piacentini and L. Pinessi and P. Roques and C. Ruiz and J. Swearer and Tanzi, {R. E.} and A. Vandenberghe and M. Vartanian and G. Vaula and Watkins, {P. C.} and R. Williamson",
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T1 - Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder

AU - St George-Hyslop, P. H.

AU - Haines, J. L.

AU - Farrer, L. A.

AU - Polinsky, R.

AU - Van Broeckhoven, C.

AU - Goate, A.

AU - Crapper McLachlan, D. R.

AU - Orr, H.

AU - Bruni, A. C.

AU - Sorbi, S.

AU - Rainero, I.

AU - Foncin, J. F.

AU - Pollen, D.

AU - Cantu, J. M.

AU - Tupler, R.

AU - Voskresenskaya, N.

AU - Mayeux, R.

AU - Growdon, J.

AU - Fried, V. A.

AU - Myers, R. H.

AU - Nee, L.

AU - Backhovens, H.

AU - Martin, J. J.

AU - Rossor, M.

AU - Owen, M. J.

AU - Mullan, M.

AU - Percy, M. E.

AU - Karlinsky, H.

AU - Rich, S.

AU - Heston, L.

AU - Montesi, M.

AU - Mortilla, M.

AU - Nacmias, N.

AU - Gusella, J. F.

AU - Hardy, J. A.

AU - Abe, Koji

AU - Amaducci, L.

AU - Bergamini, L.

AU - Bruyland, M.

AU - Cappa, S.

AU - Connor, L.

AU - De Winter, G.

AU - Drachman, D.

AU - Feldman, R. G.

AU - Fracarro, M.

AU - Franco, M. E.

AU - Frommelt, P.

AU - Gavrilova, S. I.

AU - Gei, G.

AU - Gheuens, J.

AU - Haynes, A.

AU - Henry, J.

AU - James, L.

AU - James, M. F.

AU - O'Donnell, B.

AU - Piacentini, S.

AU - Pinessi, L.

AU - Roques, P.

AU - Ruiz, C.

AU - Swearer, J.

AU - Tanzi, R. E.

AU - Vandenberghe, A.

AU - Vartanian, M.

AU - Vaula, G.

AU - Watkins, P. C.

AU - Williamson, R.

PY - 1990/9/13

Y1 - 1990/9/13

N2 - 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 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 predominantly 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 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.

AB - 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 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 predominantly 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 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.

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