EMBO: There is increasing evidence that post-traumatic stress disorder (PTSD) increases the risk of developing dementia later in life. Researchers at the University Medical Center Göttingen, Germany, now shed light on the molecular mechanism that links the two disorders. The research is published today in The EMBO Journal.
PTSD is a brain disorder that can occur after experiencing a
traumatic event. Individuals with PTSD frequently relive the traumatic
event, often triggered by stimuli similar to those that accompanied the
trauma. A number of epidemiological studies have shown that individuals
suffering from PTSD are more prone to acquiring Alzheimer’s disease
later in their lives.
Unravelling the molecular underpinnings of this correlation will help
to identify targeted therapies. The research team in Göttingen
identified such a molecular link by showing that Formin 2 is deregulated
in PTSD and Alzheimer’s disease patients. To investigate this link
further, the researchers showed that Formin 2 mutant mice show PTSD
phenotypes at an early age and develop age-related memory decline. On
the molecular level, Formin 2 is active in the brain, where it regulates
the dynamics of the cytoskeleton, the structure that helps cells to
maintain their shape and internal organization. It is required for
neuronal cell contacts to change and to ease off again after they have
been strengthened by learning.
“Our hypothesis was that various risk factors eventually cause an
aberrant activation of many genes that contribute to Alzheimer’s
disease. One of these factors could be developing PTSD via a process
that involves Formin 2,” said Farahnaz Sananbenesi, lead researcher of
To test this idea, the researchers undertook a comprehensive analysis
of gene activity in Formin 2 mutant mice. Indeed, whereas young mice
lacking Formin 2 were hardly different from normal mice, a deregulation
of hundreds of genes built up as they aged. The researchers also found
that the drug Vorinostat, which ameliorates PTSD phenotypes in younger
mice, enhanced memory in aged Formin 2-deficient mice.
“Our results indicate that it may be possible to develop therapeutic
strategies for PTSD patients that, at the same time, lower the risk to
develop Alzheimer’s disease,” said André Fischer who coordinated the
study together with Dr. Sananbenesi.
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia
Roberto Carlos Agís-Balboa, Paulo Pinhero, 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
Read the paper: DOI 10.15252/embj.201796821