TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)
Research output: Contribution to journal › Journal article › Research › peer-review
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
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.
|Journal||Neurobiology of Aging|
|Number of pages||7|
|Publication status||Published - Nov 2017|
- 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