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. 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; K. 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

doi:10.1038/347194a0

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, K. 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

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Abstract

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 phenotype^1,2. 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.

Original language	English
Pages (from-to)	194-197
Number of pages	4
Journal	Nature
Volume	347
Issue number	6289
DOIs	https://doi.org/10.1038/347194a0
State	Published - 1990
Externally published	Yes

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St. George-Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Van Broeckhoven, C., 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., ... Williamson, R. (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature, 347(6289), 194-197. https://doi.org/10.1038/347194a0

@article{47061e2f0f6d43da982c34fa917e859c,

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 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.",

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 McLachlan, {D. R.Crapper} 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 K. 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",

year = "1990",

doi = "10.1038/347194a0",

language = "English",

volume = "347",

pages = "194--197",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "6289",

}

St. George-Hyslop, PH, Haines, JL, Farrer, LA, Polinsky, R, Van Broeckhoven, C, Goate, A, McLachlan, DRC, 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. https://doi.org/10.1038/347194a0

TY - JOUR

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 - McLachlan, D. R.Crapper

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, K.

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

Y1 - 1990

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025179972&partnerID=8YFLogxK

U2 - 10.1038/347194a0

DO - 10.1038/347194a0

M3 - Article

C2 - 2395471

AN - SCOPUS:0025179972

SN - 0028-0836

VL - 347

SP - 194

EP - 197

JO - Nature

JF - Nature

IS - 6289

ER -

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

Abstract

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