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Recent Advances in the Genetics of Frontotemporal Dementia

  • Daniel W. Sirkis
  • Ethan G. Geier
  • Luke W. Bonham
  • Celeste M. Karch
  • Jennifer S. YokoyamaEmail author
Neurogenetics and Psychiatric Genetics (C Cruchaga and C Karch, Section Editors)
  • 12 Downloads
Part of the following topical collections:
  1. Topical Collection on Neurogenetics and Psychiatric Genetics

Abstract

Purpose of Review

In this review, we highlight recent advances in the human genetics of frontotemporal dementia (FTD). In addition to providing a broad survey of genes implicated in FTD in the last several years, we also discuss variation in genes implicated in both hereditary leukodystrophies and risk for FTD (e.g., TREM2, TMEM106B, CSF1R, AARS2, NOTCH3).

Recent Findings

Over the past 5 years, genetic variation in approximately 50 genes has been confirmed or suggested to cause or influence risk for FTD and FTD-spectrum disorders. We first give background and discuss recent findings related to C9ORF72, GRN, and MAPT, the genes most commonly implicated in FTD. We then provide a broad overview of other FTD-associated genes and go on to discuss new findings in FTD genetics in East Asian populations, including pathogenic variation in CHCHD10, which may represent a frequent cause of disease in Chinese populations. Finally, we consider recent insights gleaned from genome-wide association and genetic pleiotropy studies.

Summary

Recent genetic discoveries highlight cellular pathways involving autophagy, the endolysosomal system, and neuroinflammation and reveal an intriguing overlap between genes that confer risk for leukodystrophy and FTD.

Keywords

Frontotemporal lobar degeneration Leukodystrophy Genetics Autophagy Lysosomes Inflammation 

Notes

Acknowledgements

We thank Lin Yuan (UCSF) for her helpful reading of the manuscript.

Funding information

Primary research support in the Yokoyama lab is provided by the Rainwater Charitable Foundation, the Bluefield Project to Cure FTD, the Association for Frontotemporal Degeneration Susan Marcus Memorial Fund Clinical Research Grant, the Larry L. Hillblom Foundation (2016-A-005-SUP), the National Institute on Aging (K01 AG049152), and the John Douglas French Alzheimer’s Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

Daniel W. Sirkis, Ethan G. Geier, Luke W. Bonham, Celeste M. Karch, and Jennifer S. Yokoyama each declare no potential conflicts of interest.

Human and Animal Rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Daniel W. Sirkis
    • 1
  • Ethan G. Geier
    • 1
  • Luke W. Bonham
    • 1
  • Celeste M. Karch
    • 2
  • Jennifer S. Yokoyama
    • 1
    Email author
  1. 1.Memory and Aging Center, Department of NeurologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Hope Center for Neurological Disorders, Department of PsychiatryWashington University School of MedicineSt. LouisUSA

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