Study Confirms Molecular Link Between PTSD and Alzheimer's
Evidence suggests that PTSD in early childhood may lead to a higher risk of developing Alzheimer's disease.
An increasing amount of evidence suggests a link between post-traumatic stress disorder (PTSD) during early childhood and a higher probability of developing Alzheimer’s in old age. For the longest time, this theory remained just that--a theory. However, a more recent study may have discovered a molecular link between these two conditions, giving the theory new ground to support it.
At first, researchers discovered through a number of studies that the incidence of Alzheimer’s was higher in people who suffered from any neuropsychiatric disease during their childhood, especially PTSD. Veterans, in particular, were interesting subjects for study, as scientists observed that the incidence of Alzheimer’s disease before the age of 65 was double than that of the civilian population.
The link between these two conditions remained a mystery, until now. Researchers from the University Medical Center Goettingen in Germany juncovered a new piece of the puzzle, which might suggest a molecular link between both conditions. The study was published in the EMBO Journal.
Alzheimer’s is a neurodegenerative condition characterized by memory loss, a change in personality, and increasing difficulty in performing basic tasks. These symptoms are brought by an amyloid plaque buildup in the patient’s brain, which causes a reduction in brain matter as its replaced by the plaque, and a subsequent reduction in the person’s cognitive and physical capabilities. The disease is incurable, though its progression can be slowed down if detected early, through the use of medication. However, this outcome is inevitably the same. Each patient has around 8 to 9 years of life after the diagnosis. After some time has passed, the plaque will develop to a point that the areas of the brain in charge of life-sustaining vital functions become compromised, thus causing their death.
The mechanism behind the onset of Alzheimer’s is still a mystery. Scientists have only managed to identify potential risk factors that could increase the probability of developing it. Similarly, the causes behind the propagation of amyloid plaque within the brain are also unknown.
Post-traumatic stress disorder, on the other hand, is a mental disorder characterized by recurrent intrusive disturbing thoughts, feelings, or dreams related to a traumatic event. Other symptoms can include mental or physical distress to trauma-related triggers, as well as repeated attempts (conscious or otherwise) to avoid trauma-related cues. The disease can cause alterations in the way a person thinks and feels, as well as modify their fight or flight response. According to the DSM-IV, these symptoms last for well over a month. In the case of young children, they are less likely to show visible signs of distress but, instead, could manifest their traumatic memories through play.
Up until recently, PTSD was only associated with a higher risk of suicide and self-harm. However, it was recently discovered that the aberrant activation of genes due to PTSD can contribute towards the development of Alzheimer’s disease, according to Dr. Farahnaz Sananbenesi, the co-author of the study. To prove the validity of their theory, the team set out to screen for genes in animals that were induced with PTSD-like symptoms during their early life, and subsequently suffered from memory and cognitive impairment as they aged, along with an amyloid deposition in their brains.
Through this screening, scientists were able to identify one gene, Formin 2 (Fmn2), which is believed to be associated in actin cytoskeleton organization in the brain, as well as an intellectual disability that stems from mutations of this gene. The term cytoskeleton is used to refer to the “skeleton” of the cell, which is a structure that grants the organism its shape and allows it to maintain its internal organization. From this discovery, the team genetically-engineered a new batch of mice so that their Fmn2 genes were silenced, and then subjected them, as well as a healthy control group, to fear conditioning at the age of 3 months. Lastly, they also subjected the mice to memory tests.
According to the study's authors, “In the young mouse models, the team showed that a loss of Fmn2 leads to PTSD-like phenotypes as well as to ‘accelerated age-associated memory decline’ over time.” In this sense, the mice that had been treated to develop amyloid pathology also experienced a dramatic increase in the buildup of deregulated genes toward old age. This discovery suggests that PTSD contributes to the development of Alzheimer’s disease through aberrant gene expression.
This discovery may give hope for a future cure if the results could be successfully applied to human subjects. After discovering the relationship between PTSD and Alzheimer’s in mice, the team set out to test the effects of a drug called Vorinostat, which an approved HDAC-inhibitor known to improve memory. They divided the PTSD mice into two groups, and subjected them to either the drug or a placebo, for 4 weeks. After analyzing the results, the team found that the drug prevented cognitive decline in older mice. Specifically, it improved the symptoms of subjects that were both old and had the Fmn2 gene muted.
"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 Alzheimer's disease," the researchers told Medical News Today in an interview. They are already researching new treatment options using Vorinostat. They went on, "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."
The results obtained through their study shed light on new topics of interest for future projects, revolving around the experimentation on other aberrant genes that could contribute to the development of not only PTSD but of other neuropsychiatric diseases as well. They theorize that, if PTSD can trigger the abnormal activation of elements that can contribute towards Alzheimer’s disease in old age, other diseases might be able to do so as well. The team is also leaning towards the study of major depressive disorder, a condition that is becoming increasingly frequent.
