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

Rostgaard, Nina ; Roos, Peter ; Budtz-Jørgensen, Esben ; Johannsen, Peter ; Waldemar, Gunhild ; Nørremølle, Anne ; Lindquist, Suzanne G. ; Gydesen, Susanne ; Brown, Jeremy M. and Collinge, John , et al. (2017) In Neurobiology of Aging 59. p.1-221
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... (More)

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.

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keywords
ApoE, Autosomal dominantly inherited frontotemporal dementia, CHMP2B, FTD-3, SNP rs3173615, TMEM106B
in
Neurobiology of Aging
volume
59
pages
1 - 221
publisher
Elsevier
external identifiers
  • scopus:85028749703
  • pmid:28888721
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2017.06.026
language
English
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yes
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c0d8d2e4-9b56-42c6-9501-95afdda64817
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2019-06-29 22:55:16
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2020-01-16 04:01:03
@article{c0d8d2e4-9b56-42c6-9501-95afdda64817,
  abstract     = {<p>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.</p>},
  author       = {Rostgaard, Nina and Roos, Peter and Budtz-Jørgensen, Esben and Johannsen, Peter and Waldemar, Gunhild and Nørremølle, Anne and Lindquist, Suzanne G. and Gydesen, Susanne and Brown, Jeremy M. and Collinge, John and Isaacs, Adrian M. and Nielsen, Troels T. and Nielsen, Jørgen E.},
  issn         = {0197-4580},
  language     = {eng},
  month        = {11},
  pages        = {1--221},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2017.06.026},
  doi          = {10.1016/j.neurobiolaging.2017.06.026},
  volume       = {59},
  year         = {2017},
}