More and more evidence is suggesting that developing post-traumatic stress disorder early in life can raise the risk of dementia in old age. New research finds a molecular link between the two conditions, which paves the way for new therapies.
An increasing number of epidemiological
For instance, large studies in veterans in the United States have indicated that soldiers who had PTSD in their youth were
But until now, the mechanisms behind this link have not been elucidated. However, researchers from the University Medical Center Goettingen in Germany just moved closer to understanding this mechanism, as they uncover a molecular link between the two conditions.
The results of the new study were published in The EMBO Journal.
“Our hypothesis was that various risk factors eventually cause an aberrant activation of many genes that contribute to Alzheimer’s disease,” explains Dr. Farahnaz Sananbenesi, who jointly lead the research with Prof. André Fischer.
The team set out to screen for genes in animal models that have PTSD-like symptoms in early life, but which experience memory impairment as they age when exposed to additional Alzheimer’s disease risk factors such as amyloid deposition.
Through this screening, the researchers identified the Formin 2 (Fmn2) gene, which is
The team genetically modified mice so that their Fmn2 genes were silenced. They exposed the mutant mice – as well as a control group – to fear conditioning starting at the age of 3 months. Additionally, they subjected the mice to memory tests.
In the young mouse models, the team showed that a loss of Fmn2 lead to PTSD-like phenotypes as well as to “accelerated age-associated memory decline” over time.
In mice that had been exposed to amyloid pathology, the researchers found a gradual but dramatic increase in the buildup of deregulated genes toward old age. This suggests, therefore, that PTSD may lead to Alzheimer’s disease through aberrant gene expression.
The researchers also examined the post-mortem human brain samples of patients with Alzheimer’s and found decreased Fmn2 expression.
“Our data provide insight to the molecular mechanisms by which neuropsychiatric diseases at a young age lead to an increased risk for dementia when individuals age,” the authors conclude.
When asked about the strengths and limitations of their study, the researchers told Medical News Today that:
“Since we combine work in human neurons, in blood, and in postmortem brain tissue we provide evidence that our data is indeed relevant to the human diseases. The mechanistic work, of course, was performed in mice and great care has to be taken when interpreting data from animal models in the context of human diseases.”
Furthermore, the researchers tested the effect of a drug called Vorinostat – which is an approved HDAC-inhibitor known to improve memory – in mice.
After treating mice with either Vorinostat or a placebo for 4 weeks, the researchers found that the drug prevented cognitive decline in mutant older mice – namely, mice that were 8 months old and had the Fmn2 gene knocked off.
The researchers also note directions for future research, suggesting that their experimental model should be used to continue to test other genes and environmental factors that contribute to PTSD or other neuropsychiatric conditions.
For instance, the researchers would like to test their hypothesis for other conditions that have been linked to Alzheimer’s disease, such as major depression.
“Our study now provides first insight to these mechanisms and offers – via the use of HDAC inhibitors – therapeutic options that should help people with PTSD and AD [Alzheimer’s disease],” the researchers told MNT.
In fact, the team is already hard at work exploring these new options. They said, “We have initiated a clinical pilot study to test [if] targeting gene-expression via the HDAC inhibitor Vorinostat (the one used also in our current study) would help AD patients.”