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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
  • E. Englund (Medarbetare)
  • FReJA
Enheter & grupper
Externa organisationer
  • University of Copenhagen
  • Addenbrooke's Hospital
  • University College London
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)221.e1-221.e7
TidskriftNeurobiology of Aging
Volym59
StatusPublished - 2017 nov 1
PublikationskategoriForskning
Peer review utfördJa