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Movement Disorder Genetics pp 75–105Cite as

Genetics of Frontotemporal Dementia

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Abstract

Frontotemporal dementia (FTD) is a progressive brain disease characterized by atrophy of the frontal and anterior temporal lobes. The prevalence has been estimated between 10 and 30 per 100,000, and patients have severe changes in personality and behavior. The disease has a strong genetic component, and in up to 40 % of cases, a positive family history has been observed. To date, seven disease genes have been identified, of which MAPT, GRN, and C9orf72 are most frequently mutated. In contrast to familial FTD, far less is known about sporadic FTD. GWAS reported TMEM106B as an important risk factor for FTD, and recently, new loci have been associated with the disease. In this chapter, we summarize the current insights into the genetics of FTD based on neuropathological and functional data.

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Abbreviations

aFTLD-U:

Atypical frontotemporal lobar degeneration with ubiquitinated inclusions

AGD:

Argyrophilic grain disease

BIBD:

Basophilic inclusion body disease

C9orf72 :

Chromosome 9 open reading frame 72

CBD:

Corticobasal degeneration

CHMP2B :

Charged multivesicular body protein 2B

FTD-3:

Frontotemporal dementia linked to chromosome 3

FTLD:

Frontotemporal lobar degeneration

FUS :

Fused in sarcoma

GRN :

Granulin

MAPT :

Microtubule-associated protein tau

MSTD:

Multiple system tauopathy with dementia

NFT-dementia:

Neurofibrillary tangle predominant dementia

ni:

No inclusions

NIFID:

Neuronal intermediate filament inclusion disease

PiD:

Pick’s disease

PSP:

Progressive supranuclear palsy

TARDBP :

TAR DNA-binding protein

TDP:

TDP-43

UPS:

Ubiquitin proteasome system

VCP :

Valosin-containing protein

WMT-GGI:

White matter tauopathy with globular glial inclusions

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Disclosure

Peter Heutink is a co-applicant on a patent application related to MAPT (PCT/US1999/009529) and C9orf72 (PCT/GB2012/052140) and is co-owner of Synaptologics BV.

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Authors and Affiliations

  1. Genome Biology of Neurodegenerative Diseases, Tübingen, 72076, Germany

    Sasja Heetveld MSc & Peter Heutink MSc, PhD

  2. Eberhard Karls University, Tübingen, Germany

    Sasja Heetveld MSc & Peter Heutink MSc, PhD

  3. Applied Genomics of Neurodegenerative Diseases, Tübingen, 72076, Germany

    Patrizia Rizzu PhD

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  1. Sasja Heetveld MSc
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  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Heetveld, S., Rizzu, P., Heutink, P. (2015). Genetics of Frontotemporal Dementia. In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_5

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