TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

Nina Rostgaard; Peter Roos; Esben Budtz-Jørgensen; Peter Johannsen; Gunhild Waldemar; Anne Nørremølle; Suzanne G. Lindquist; Susanne Gydesen; Jeremy M. Brown; John Collinge; Adrian M. Isaacs; Troels T. Nielsen; Jørgen E Nielsen; FReJA collaboration

doi:10.1016/j.neurobiolaging.2017.06.026

TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

Nina Rostgaard, Peter Roos, Esben Budtz-Jørgensen, Peter Johannsen, Gunhild Waldemar, Anne Nørremølle, Suzanne G. Lindquist, Susanne Gydesen, Jeremy M. Brown, John Collinge, Adrian M. Isaacs, Troels T. Nielsen, Jørgen E Nielsen, FReJA collaboration

4 Citationer (Scopus)

Abstract

Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Aging
Vol/bind	59
Sider (fra-til)	221.e1-221.e7
Antal sider	7
ISSN	0197-4580
DOI	https://doi.org/10.1016/j.neurobiolaging.2017.06.026
Status	Udgivet - nov. 2017

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10.1016/j.neurobiolaging.2017.06.026

Citationsformater

Rostgaard, N., Roos, P., Budtz-Jørgensen, E., Johannsen, P., Waldemar, G., Nørremølle, A., Lindquist, S. G., Gydesen, S., Brown, J. M., Collinge, J., Isaacs, A. M., Nielsen, T. T., Nielsen, J. E., & FReJA collaboration (2017). TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3). Neurobiology of Aging, 59, 221.e1-221.e7. https://doi.org/10.1016/j.neurobiolaging.2017.06.026

Rostgaard, N, Roos, P, Budtz-Jørgensen, E, Johannsen, P, Waldemar, G , Nørremølle, A, Lindquist, SG, Gydesen, S, Brown, JM, Collinge, J, Isaacs, AM, Nielsen, TT, Nielsen, JE & FReJA collaboration 2017, 'TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)', Neurobiology of Aging, bind 59, s. 221.e1-221.e7. https://doi.org/10.1016/j.neurobiolaging.2017.06.026

@article{b4f00c23ec6143ed8e3aa991f36f303c,

title = "TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)",

abstract = "Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.",

keywords = "Adult, Aged, Aged, 80 and over, Apolipoprotein E2, Disease Progression, Endosomal Sorting Complexes Required for Transport, Female, Frontotemporal Dementia, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Risk Factors, Journal Article",

author = "Nina Rostgaard and Peter Roos and Esben Budtz-J{\o}rgensen and Peter Johannsen and Gunhild Waldemar and Anne N{\o}rrem{\o}lle and Lindquist, {Suzanne G.} and Susanne Gydesen and Brown, {Jeremy M.} and John Collinge and Isaacs, {Adrian M.} and Nielsen, {Troels T.} and Nielsen, {J{\o}rgen E} and {FReJA collaboration}",

year = "2017",

month = nov,

doi = "10.1016/j.neurobiolaging.2017.06.026",

language = "English",

volume = "59",

pages = "221.e1--221.e7",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier",

}

TY - JOUR

T1 - TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

AU - Rostgaard, Nina

AU - Roos, Peter

AU - Budtz-Jørgensen, Esben

AU - Johannsen, Peter

AU - Waldemar, Gunhild

AU - Nørremølle, Anne

AU - Lindquist, Suzanne G.

AU - Gydesen, Susanne

AU - Brown, Jeremy M.

AU - Collinge, John

AU - Isaacs, Adrian M.

AU - Nielsen, Troels T.

AU - Nielsen, Jørgen E

AU - FReJA collaboration

PY - 2017/11

Y1 - 2017/11

N2 - Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.

AB - Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Apolipoprotein E2

KW - Disease Progression

KW - Endosomal Sorting Complexes Required for Transport

KW - Female

KW - Frontotemporal Dementia

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Membrane Proteins

KW - Middle Aged

KW - Mutation

KW - Nerve Tissue Proteins

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Journal Article

U2 - 10.1016/j.neurobiolaging.2017.06.026

DO - 10.1016/j.neurobiolaging.2017.06.026

M3 - Journal article

C2 - 28888721

SN - 0197-4580

VL - 59

SP - 221.e1-221.e7

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

Abstract

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