Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia

Roberto Carlos Agís‐Balboa, Paulo S Pinheiro, Nelson Rebola, Cemil Kerimoglu, Eva Benito, Michael Gertig, Sanaz Bahari‐Javan, Gaurav Jain, Susanne Burkhardt, Ivana Delalle, Alexander Jatzko, Markus Dettenhofer, Patricia A Zunszain, Andrea Schmitt, Peter Falkai, Julius C Pape, Elisabeth B Binder, Christophe Mulle, Andre Fischer, Farahnaz Sananbenesi
EMBO J.. 2017-08-02; 36(19): 2815-2828
DOI: 10.15252/embj.201796821

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1. EMBO J. 2017 Oct 2;36(19):2815-2828. doi: 10.15252/embj.201796821. Epub 2017 Aug
2. Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.

Agís-Balboa RC(1), Pinheiro PS(2)(3)(4), Rebola N(2)(3), Kerimoglu C(1)(5), Benito E(1), Gertig M(1), Bahari-Javan S(5), Jain G(1), Burkhardt S(1), Delalle I(4), Jatzko A(6), Dettenhofer M(7), Zunszain PA(8), Schmitt A(9)(10), Falkai P(9), Pape JC(11), Binder EB(11), Mulle C(2)(3), Fischer A(12)(5), Sananbenesi F(12)(13).

Author information:
(1)Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, Göttingen, Germany.
(2)Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, France.
(3)CNRS UMR 5297, Bordeaux, France.
(4)Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
(5)Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
(6)Department of Psychosomatics, Westpfalzklinikum-Kaiserslautern, Teaching Hospital, University of Mainz, Mainz, Germany.
(7)CEITEC – Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
(8)Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK.
(9)Department of Psychiatry and Psychotherapy, LMU Munich, Munich, Germany.
(10)Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo, São Paulo, Brazil.
(11)Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
(12)Department for Epigenetics and Systems Medicine in Neurodegenerative  Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, Göttingen, Germany .
(13)Research Group for Genome Dynamics in Brain Diseases, Göttingen, Germany.

Comment in
EMBO J. 2017 Oct 2;36(19):2809-2811.

Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer’s disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia.

© 2017 The Authors. Published under the terms of the CC BY 4.0 license.

DOI: 10.15252/embj.201796821
PMCID: PMC5623844
PMID: 28768717 [Indexed for MEDLINE]

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