While each person experiences a slightly different set of symptoms, the first noticeable symptoms of Alzheimer’s disease in most people is typically memory loss and difficulty in finding words in both speech and writing. Because such lapses are common and a normal part of ageing, the onset of the illness may not be recognised immediately.
As the disease progresses, people around the affected person may begin to notice signs of the disease. The person with Alzheimer’s disease may begin to find it difficult to plan and organise, for example keeping track of monthly finances, and have less knowledge or memory of recent events. They may become withdrawn.
Later in the disease larger deficits in thinking and thought processes may appear, for example difficulties with basic mental arithmetic or inability to remember important personal details, such as their address. The affected person may become confused about where they are or what day it is.
In the severe stages of the disease, the affected person’s personality and behaviour may change. They may experience delusions and hallucinations, have disrupted sleep patterns and need help with dressing and toileting.
We don’t know what causes Alzheimer’s disease. Risk factors include age, having a first degree relative with the disease, having had a head injury in the past, and having low levels of physical activity, hypertension, diabetes, high cholesterol or atrial fibrillation.
There are two types of Alzheimer’s disease: early-onset and late-onset. Early-onset Alzheimer’s disease is rare, affecting only about 5% of people with the disease. People with the early-onset form usually develop the disease between the ages of 30 and 60. Late-onset Alzheimer’s disease makes up the bulk of cases, and affects people after the age of 60.
Although we are still teasing out the details, we know that genetic factors play some role in the disease as people with an affected first degree relative are at a higher risk of developing the disease. The only genetic risk factor that we know of so far for developing late-onset Alzheimer’s disease is a particular form of the ApoE protein gene (called the ApoE e4 allele).
Early-onset Alzheimer’s disease also has genetic links. A particular type, called familial Alzheimer’s disease, is caused by one of three known genetic mutations. Children of affected people have a 50% chance of inheriting their parent’s genetic mutation; those that do will almost certainly develop the disease. The mutations we know of so far are in the genes for amyloid precursor protein (APP), presenilin 1 (PS1) or presenilin 2 (PS2). These mutations cause abnormal proteins to form in the brain, which leads to an increased amount of a protein called beta amyloid.
All people with Alzheimer’s disease – both early and late-onset – have been found to have an abnormal build-up of this protein in their brains, which clusters between the brain cells in what we call plaques. Another protein called tau forms what we call tangles inside the brain cells.
While researchers have shown that the amount of these proteins in the brain corresponds with the severity of symptoms in Alzheimer’s disease, we don’t yet understand the role of beta amyloid and tau in the disease process.
We do not yet have a cure for Alzheimer’s disease. However, there are several drug treatments that can help alleviate the symptoms of the disease.
Acetylcholine Esterase Inhibitors (also known as cholinesterase inhibitors) prevent the breakdown of acetylcholine, a neurotransmitter that is important for memory and attention. NMDA receptor antagonists prevent the over-activity of a neurotransmitter called glutamate, which is also involved in learning and memory.
Right now, researchers are working to understand the biological basis of the disease so we can develop new treatments that target the cause, not just the symptoms.
About our research
We are working on three different aspects of tissue changes associated with Alzheimer’s disease that we believe may be amenable to new treatments.
The first is based on observations that people taking anti-hypertensive medications are less likely to have Alzheimer’s disease. Andrew Affleck is investigating why this occurs at the tissue level. In particular, which anti-hypertensive medications are effective, and whether they have a direct effect on receptors in the brain tissue, or whether they affect the flow of blood to the brain. It is hoped this work may provide evidence for therapeutically changing the tissue pathology underlying Alzheimer’s disease.
The second type of study is based on recent genetic studies that have identified the gene ABCA7 as a strong risk factor for Alzheimer’s disease, although the biological reason for this is unknown. Scott Kim has data from cell model studies that ABCA7 plays a protective role in the brain – it is a protein important for the cells that clear the neurotoxic proteins forming the tissue plaques in the brains of patients with Alzheimer’s disease. Scott’s new research will determine whether ABCA7 is important in animal models of Alzheimer’s disease and in human brain tissue samples from patients. He will also use the animal models to assess whether he can manipulate the protein to reduce the tissue pathology of Alzheimer’s disease.
Lastly, we are performing a number of studies on inflammation in the brain tissue of patients with Alzheimer’s disease in the hope that we can determine targets that can be manipulated therapeutically. Brain inflammation in Alzheimer’s disease is harmful and results in cell loss and dysfunction. Surabi Bhatia is looking at an evolutionary conserved protein with antioxidant properties called Apolipoprotein D (ApoD). Her work is to assess whether the levels of this protein are related to the degree of inflammation in the brain of patients with Alzheimer’s disease. Claire Shepherd is working on identifying the proteins that cause the inflammation using brain tissue samples from patients as well as cellular models of the disease.
Could there be a potential link between high blood pressure (hypertension) and the brain tissue changes responsible for dementia? PhD Student and Sydney Brain Bank staff member, Andrew Affleck elaborates on his research. Over the past few months I have been approached by a number of family and friends, mostly curious to see how my PhD is progressing. Some […]