Progressive supranuclear palsy (PSP) is a rare brain disorder that affects approximately 6 in 100,000 people worldwide. It causes muscle weakness and affects gait, balance and overall movement, as well as mood, cognitive skills and behavior. It is a neurodegenerative disorder classified as a “tauopathy”, as it is associated with the pathological aggregation of tau protein in the brain. PSP remains a subject of intense research, which is spurred by the hope of finding a root cause for this and other similar neurodegenerative disorders in the near future.
Mechanism of PSP
Progressive supranuclear palsy develops when brain cells in certain areas of the brain start to gradually deteriorate. In particular, some parts of the brain responsible for cognitive skills (the frontal lobe) and others dealing with gait and balance (the midbrain) seem to be affected. The mechanism that causes PSP is not fully known. Most cases seem to appear spontaneously with no previous family history of neurodegenerative disorders.
An important area of the brain called the substantia nigra seems to be affected in PSP. It is located in the midbrain and is responsible for reward in general, and movement in particular. A similar situation occurs in other neurological disorders, particularly in Parkinson’s disease. This is the reason why these two disorders exhibit some of the same symptoms and may be mistaken for one another. Studies show a loss of dopaminergic neurons (i.e. neurons for which dopamine acts as a neurotransmitter) in the substantia nigra in patients suffering from Parkinson’s disease. No similar conclusive links have been found with regard to PSP, however, until now.
Gene Mutations in PSP
PSP (and other neurodegenerative disorders) has been linked to mutations in the MAPT gene, which encodes for a type of protein called tau. In PSP, it appears that there are pathological amounts of tau protein aggregating in the brain. This type of protein occurs normally, but is usually broken down before it reaches potentially damaging levels in the brain. Particularly the parts of the brain that are involved in controlling movement (the midbrain) and thinking (the frontal lobe) are affected in PSP. Various areas may be affected to different degrees, and as such, patients may exhibit varying symptoms of the disease.
Tau protein build-up is also linked to other neurodegenerative disorders including Parkinson’s disease. However, no conclusive evidence has been found for a direct link between tau protein and progressive supranuclear palsy.
Interestingly, pathological tau protein is also found in PSP sufferers who don't exhibit MAPT mutations. This has led researchers to believe that environmental factors play a role in the development of the disorder.
The only risk factor established so far for PSP is advanced age. PSP usually begins to be symptomatic around the age of 60 years, and is unknown under the age of 40. However, there is some evidence to show that certain chemicals in the environment or diet may contribute to PSP. Additionally, exposure to significant life stressors may be associated with the development of PSP
No conclusive evidence has been found so far to classify PSP as a genetic disease. It is usually a sporadic condition (not inherited), occurring in people with no family history of PSP. Rarely PSP occurs as a familial (inherited, genetically-determined) disease.