Down syndrome patients have increased in recent decades, partly owing to advancement in patient care and treatment. Nevertheless, these individuals, who live in the fifth and sixth years of life, are now susceptible to complications related to ageing, primarily due to impairments in thinking. These are also known for their involvement in Alzheimers disease.
In addition, some studies claim that the decreased efficiency of a key protein transport system, which plays a crucial role in clearing damaged and degraded proteins from neurons in the brain, is partly to blame. In addition, the researchers found that the so-called retromer complex system, which plays a vital role in clearing damaged and degrading proteins from the brain, operates at only about 50 percent of its usual efficiency in Down syndrome patients. This was particularly related to the accumulation of pathogenic tau protein.
The decline in protein transport via the retromer system is similar to a traffic jam, with the transporter stalling out and causing a large back-up in the clearance of pathologic tau proteins, which have been left to accumulate during the time, according to Doctor Domenico Pratico, MD, a professor at the Department of Neural Sciences, and the Alzheimers Center at Temple. A senior investigator has been interviewed by the research.
According to Dr. Pratico, tau accumulation is linked to a decrease in the activity of the cathepsin-D enzyme, which resides within the retromer complex. Cathepsin-D normally acts like a pair of scissors, cutting tau to facilitate its digestion and removal.
The study, published online in the journalAnnals of Neurology, is the first to investigate how reductions in retromer system efficiency and cathepsin-D activity are not directly linked to the accumulation of pathogenic tau in Down syndrome. These findings are significant because they suggest that Alzheimer-like changes are not strictly modulated by the extra chromosome 21 that is characteristic of Down syndrome. While the extra chromosome increases the risk of amyloid plaque formation, not all Down syndrome patients develop dementia, implicating the involvement of
Dr. Pratico and his colleagues first measured the extent of tau pathology in brain tissue from patients with Down syndrome and then examined the relationship between the retromer core protein levels and the amount of pathologic tau protein in young and aged individuals with Down Syndrome. They also examined the activity of cathepsin-D and the amount of tau pathology in the same individuals.
The teams observed an inverse relationship between the formation of tau pathology in Down syndrome and the levels of retromer proteins, according to the findings. Moreover, the reduced levels of retromer proteins in young Down syndrome subjects set the stage for the development of tau pathology later in life.
As per Dr. Pratico, the retromer complex is a key regulator of pathogenic tau in Down syndrome. There is evidence for the development of tau pathology at a relatively young age.
The results suggest that the retromer system is also a promising new approach for Alzheimers disease pathology in Down syndrome patients. In future experiments, Dr. Pratico and his colleagues intend to investigate these possibilities in animal models that replicate the majority of the features of Down syndrome observed in humans.
As we utilize these existing therapies, we want to see if it is possible to reverse amyloid plaque and pathological tau accumulation in animal models, according to Dr. Pratico. We will have created an exciting opportunity to investigate treatments in human patients with Down syndrome.