TY  - JOUR
AU  - Agís-Balboa, Roberto Carlos
AU  - Pinheiro, Paulo S
AU  - Rebola, Nelson
AU  - Kerimoglu, Cemil
AU  - Benito, Eva
AU  - Gertig, Michael
AU  - Bahari-Javan, Sanaz
AU  - Jain, Gaurav
AU  - Burkhardt, Susanne
AU  - Delalle, Ivana
AU  - Jatzko, Alexander
AU  - Dettenhofer, Markus
AU  - Zunszain, Patricia A
AU  - Schmitt, Andrea
AU  - Falkai, Peter
AU  - Pape, Julius C
AU  - Binder, Elisabeth B
AU  - Mulle, Christophe
AU  - Fischer, Andre
AU  - Sananbenesi, Farahnaz
TI  - Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.
JO  - The EMBO journal
VL  - 36
IS  - 19
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2020-05853
SP  - 2815-2828
PY  - 2017
AB  - 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.
KW  - Adult
KW  - Age of Onset
KW  - Aging: genetics
KW  - Aging: physiology
KW  - Animals
KW  - Case-Control Studies
KW  - Dementia: epidemiology
KW  - Dementia: genetics
KW  - Dementia: psychology
KW  - Formins
KW  - Humans
KW  - Male
KW  - Memory: physiology
KW  - Mice
KW  - Mice, Knockout
KW  - Microfilament Proteins: genetics
KW  - Middle Aged
KW  - Nerve Tissue Proteins
KW  - Neuronal Plasticity: genetics
KW  - Nuclear Proteins: genetics
KW  - Phenotype
KW  - Risk Factors
KW  - Stress Disorders, Post-Traumatic: complications
KW  - Stress Disorders, Post-Traumatic: epidemiology
KW  - Stress Disorders, Post-Traumatic: genetics
KW  - Formins (NLM Chemicals)
KW  - Microfilament Proteins (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - formin 2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28768717
C2  - pmc:PMC5623844
DO  - DOI:10.15252/embj.201796821
UR  - https://pub.dzne.de/record/139531
ER  -