The Science Bit: Part 8 – Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder that affects almost 30 million people around the world. Characterised by worsening forgetfulness, confusion and mood swings, it is a heartbreaking condition both for the sufferer and for their loved ones. Though there is currently no known cure for Alzheimer’s disease, several scientific breakthroughs have recently been made that provide encouraging insights into the disease and developments in diagnosis.

Alzheimer’s disease, a type of dementia most often seen in people over the age of 65, seems to be caused by the build-up of structures called amyloid plaques and neurofibrillary tangles in the brain. These plaques and tangles are formed from fragments of proteins that would normally be broken down into harmless substances and recycled into new molecules, but a faulty mechanism in people with Alzheimer’s disease seems to cause these protein fragments to bundle together in hard, insoluble structures that lodge in between and around nerve cells in the memory cortex of the brain. As a result of both amyloid plaques and neurofibrillary tangles, the normal transport connections are inactivated and nerve cells begin to die.

A primary research target into understanding more about Alzheimer’s disease is to look at the reasons why these proteins go wrong. Since proteins are the products of genes, genetic investigation is key and so far, at least 4 different genes have been implicated. Researchers are also very interested in the link between Alzheimer’s and Down’s Syndrome, since people with this chromosome disorder tend to age more quickly than most people and also suffer from Alzheimer’s-like symptoms. In fact, a study from the UT Southwestern Medical Center earlier this year (Netzer et al., PLoS One 5(6): e10943) found that reducing the levels of an Alzheimer’s-related protein in the brain seems to improve the ability for mice with a Down’s-like syndrome to learn.

Another line of enquiry looks at the relationship between cholesterol and Alzheimer’s disease. Cholesterol is usually thought of a “bad” substance that causes heart disease, but a certain amount of cholesterol is actually essential for the synthesis of the cell membranes. Smaller amounts of excess cholesterol in the blood is usually broken down into chemicals called oxysterols, which in turn are then eliminated in the liver and further broken down into harmless substances. Researchers have discovered that people with Alzheimer’s disease seem to have higher levels of certain types of oxysterols in their blood, which suggests that there may be a connection between a faulty cholesterol metabolism and brain degeneration. Building a profile of the types and levels of oxysterol in a person’s blood may help doctors to diagnose Alzheimer’s more quickly.

The most recent breakthrough in Alzheimer’s research, published in Cell this month (Reddy et al., Cell 144(1), 132-142), comes from a team at the Scripps Research Institute which has developed a new way to identify diseases, including Alzheimer’s disease. Using thousands of different synthetic molecules called “peptoids”, the team were able to identify disease-specific biomarkers in mouse blood samples. It is hoped that now, by passing the technique over to Alzheimer’s experts, further research may one day lead to the development of a simple blood test that will identify these biomarkers for Alzheimer’s disease in individuals who have yet to show symptoms, thus allowing earlier diagnosis and treatment.