Surgery News

Prion infection of neurons increases the free cholesterol content in cell membranes

October 14, 2015

It is widely believed that prions (protein only infectious material) are the cause of rare progressive neurodegenerative disorders that affect both humans and animals. A prion is an infectious agent made solely of protein. However what is not known is how the prions damage brain cells (neurons).

Dr Clive Bate and colleagues from the Royal Veterinary College in the UK compared the amounts of protein and cholesterol in prion-infected neuronal cell lines and primary cortical neurons with uninfected controls. Protein levels were similar but the amount of total cholesterol (a mixture of free and esterified cholesterol) was significantly higher in the infected cell lines. The cholesterol balance was also affected: the amount of free cholesterol increased but that of cholesterol esters reduced, suggesting that prion infection affects cholesterol regulation. The team attempted to reproduce the effects of prions on cholesterol levels, by stimulating cholesterol biosynthesis or by adding exogenous cholesterol. Both approaches resulted in increased amounts of cholesterol esters but not of free cholesterol. The free cholesterol is thought to affect the function of the cell membranes and to lead to abnormal activation of phospholipase A2, an enzyme implicated in the depletion of neurons in prion and Alzheimer's disease.

Studies have recently shown that the controlling cholesterol levels within the brain is critical in limiting the development of neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases, multiple sclerosis, and senile dementia. This study now gives far more specific insight into the kind of mechanisms at work. Dr Bate stated: ???Our observations raise the possibility that disturbances in membrane cholesterol induced by prions are major triggering events in the neuropathogenesis of prion diseases???.

biomedcentral/

The difference between dementia and Alzheimer's disease is simply that Alzheimer's disease is one of the major causes of dementia but there are many others.

Alzheimer's disease is the most common form of dementia accounting for between 50% and 70% of all cases and is a physical condition which attacks the brain, resulting in impaired memory, thinking and behaviour.

As brain cells die, abnormal material builds up and as the disease progresses, long-term memory is also lost; the disease also affects many of the brain's other functions and as a result many other of behaviour.

Vascular dementia is the second most common cause accounting for up to 20% of all cases of dementia; strokes and mini strokes can cause vascular dementia, as can poor circulation of blood to the brain.

The symptoms of vascular dementia may appear similar to Alzheimer's disease.

There are other causes of dementia such as Parkinson's disease and most forms of dementia, are progressive and incurable.

Dementia affects the young as well as older people and there are 10,000 Australians with dementia who are people under 65; some are as young as 35.

High blood pressure, high cholesterol and smoking are all risk factors for the development of dementia, as well as for heart disease and eating healthily and exercising regularly are important in reducing dementia risks, as is management of diabetes and cardiovascular conditions.

Alzheimer's Australia says the findings were both surprising and encouraging.

The Pfizer Australia Health Report was produced in partnership with Alzheimer's Australia and can be accessed at www.healthreport.au