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Neurobiol Aging. 2017 Nov;59:221.e1-221.e7. doi: 10.1016/j.neurobiolaging.2017.06.026. Epub 2017 Jul 11.

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

Author information

1
Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6911, Copenhagen, Denmark.
2
Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6911, Copenhagen, Denmark. Electronic address: peter.roos@regionh.dk.
3
Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
4
Section of Neurogenetics, Institute of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
5
Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6911, Copenhagen, Denmark; Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Section 4062, Copenhagen, Denmark.
6
Department of Psychiatry, Community Mental Health Services in Region Zealand, Nykøbing Sjælland, Denmark.
7
Department of Neurology, Addenbrooke's Hospital, Cambridge, UK.
8
MRC Prion Unit, Institute of Neurology, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
9
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, UCL Institute of Neurology, London, UK.
10
Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6911, Copenhagen, Denmark; Section of Neurogenetics, Institute of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.

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:

ApoE; Autosomal dominantly inherited frontotemporal dementia; CHMP2B; FTD-3; SNP rs3173615; TMEM106B

[Indexed for MEDLINE]

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