Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

H Houlden; M Baker; H R Morris; N MacDonald; S Pickering-Brown; J Adamson; A J Lees; M N Rossor; N P Quinn; A Kertesz; M N Khan; J Hardy; P L Lantos; P St George-Hyslop; D G Munoz; D Mann; A E Lang; C Bergeron; E H Bigio; I Litvan; K P Bhatia; D Dickson; N W Wood; M Hutton

Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

H Houlden, M Baker, H R Morris, N MacDonald, S Pickering-Brown, J Adamson, A J Lees, M N Rossor, N P Quinn, A Kertesz, M N Khan, J Hardy, P L Lantos, P St George-Hyslop, D G Munoz, D Mann, A E Lang, C Bergeron, E H Bigio, I LitvanK P Bhatia, D Dickson, N W Wood, M Hutton

Division of Neuroscience

University College London (UCL)

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD).

BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD.

METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls.

RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]).

CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.

Original language	English
Pages (from-to)	1702-6
Number of pages	5
Journal	Neurology
Volume	56
Issue number	12
Publication status	Published - 26 Jun 2001

Keywords

Genotype
Haplotypes
Humans
Neurodegenerative Diseases
Polymerase Chain Reaction
Supranuclear Palsy, Progressive
tau Proteins
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Cite this

Houlden, H., Baker, M., Morris, H. R., MacDonald, N., Pickering-Brown, S., Adamson, J., Lees, A. J., Rossor, M. N., Quinn, N. P., Kertesz, A., Khan, M. N., Hardy, J., Lantos, P. L., St George-Hyslop, P., Munoz, D. G., Mann, D., Lang, A. E., Bergeron, C., Bigio, E. H., ... Hutton, M. (2001). Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology, 56(12), 1702-6.

@article{2d7cada49c284b51ad34a98f870dd3f1,

title = "Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype",

abstract = "OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD).BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD.METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls.RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]).CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.",

keywords = "Genotype, Haplotypes, Humans, Neurodegenerative Diseases, Polymerase Chain Reaction, Supranuclear Palsy, Progressive, tau Proteins, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.",

author = "H Houlden and M Baker and Morris, {H R} and N MacDonald and S Pickering-Brown and J Adamson and Lees, {A J} and Rossor, {M N} and Quinn, {N P} and A Kertesz and Khan, {M N} and J Hardy and Lantos, {P L} and {St George-Hyslop}, P and Munoz, {D G} and D Mann and Lang, {A E} and C Bergeron and Bigio, {E H} and I Litvan and Bhatia, {K P} and D Dickson and Wood, {N W} and M Hutton",

year = "2001",

month = jun,

day = "26",

language = "English",

volume = "56",

pages = "1702--6",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "12",

}

Houlden, H, Baker, M, Morris, HR, MacDonald, N, Pickering-Brown, S, Adamson, J, Lees, AJ, Rossor, MN, Quinn, NP, Kertesz, A, Khan, MN, Hardy, J, Lantos, PL, St George-Hyslop, P, Munoz, DG, Mann, D, Lang, AE, Bergeron, C, Bigio, EH, Litvan, I, Bhatia, KP, Dickson, D, Wood, NW & Hutton, M 2001, 'Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype', Neurology, vol. 56, no. 12, pp. 1702-6.

TY - JOUR

T1 - Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

AU - Houlden, H

AU - Baker, M

AU - Morris, H R

AU - MacDonald, N

AU - Pickering-Brown, S

AU - Adamson, J

AU - Lees, A J

AU - Rossor, M N

AU - Quinn, N P

AU - Kertesz, A

AU - Khan, M N

AU - Hardy, J

AU - Lantos, P L

AU - St George-Hyslop, P

AU - Munoz, D G

AU - Mann, D

AU - Lang, A E

AU - Bergeron, C

AU - Bigio, E H

AU - Litvan, I

AU - Bhatia, K P

AU - Dickson, D

AU - Wood, N W

AU - Hutton, M

PY - 2001/6/26

Y1 - 2001/6/26

N2 - OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD).BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD.METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls.RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]).CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.

AB - OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD).BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD.METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls.RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]).CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Neurodegenerative Diseases

KW - Polymerase Chain Reaction

KW - Supranuclear Palsy, Progressive

KW - tau Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

M3 - Article

C2 - 11425937

SN - 0028-3878

VL - 56

SP - 1702

EP - 1706

JO - Neurology

JF - Neurology

IS - 12

ER -

Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

Abstract

Keywords

Fingerprint

Cite this