Genetics of Frontotemporal Dementia

Chapter

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.

Keywords

C9orf72 Frontotemporal dementia Frontotemporal lobar degeneration GRN MAPT Neurodegeneration 

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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Notes

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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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Sasja Heetveld
    • 1
    • 2
  • Patrizia Rizzu
    • 3
  • Peter Heutink
    • 1
    • 2
  1. 1.Genome Biology of Neurodegenerative DiseasesTübingenGermany
  2. 2.Eberhard Karls UniversityTübingenGermany
  3. 3.Applied Genomics of Neurodegenerative DiseasesTübingenGermany

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