What is Alzheimer’s Disease?
Alzheimer’s disease is a progressive mental deterioration characterised by dementia and loss of memory. The cause of Alzheimer’s disease is unknown but the brain changes that occur involve the neuronal death of neurons that use acetylcholine and other chemicals as their neurotransmitters and the greatest loss of neurons occurs in the hippocampus and frontal cortex. Pathologically, the brain accumulates abnormal deposits of protein called amyloid plaques and tau tangles. There are however, many different types of dementia but Alzheimer’s disease is the most common form of these.
How has research helped in understanding Alzheimer’s disease?
Only by examining the human brain affected by Alzheimer’s disease has it been possible to establish which brain regions and cell types are affected by the disease. Such studies are essential for determining whether a person has Alzheimer’s disease or some other type of dementia. This is important for families as some dementias are hereditary and others are sporadic and not associated with known gene defect. Research studies have also been influential in enabling the genetics of some dementias to be determined. Whilst the majority of Alzheimer’s disease cases are sporadic there are about 15% of cases where a mutation on a single gene can predispose an individual to Alzheimer’s disease.
Understanding the earliest change in the brain in Alzheimer’s disease
Long before the loss of memory and dementia develop in Alzheimer’s disease, there have already been significant changes in the olfactory system (smell centre) in the brain. We have been performing experiments to study the earliest events that begin the neurochemical change and cell death that occurs in the olfactory bulb. These studies include detailed reconstructions of the olfactory system, identifying the cell types most severely affected and detailing the number, size and shape of the active units that control the ability to smell (called glomeruli). These studies are being performed in collaboration with a world leading group in Germany who are experts on olfaction. We believe that only when we understand the origins of the disease will we be able to intervene early to possibly stop the onset and to slow the disease progression.
Growing brain cells from brain tissue
Recent work in our laboratories have revealed that human brain cells can be kept alive in cell culture conditions for up to a year after someone dies and donates their brain to the Brain Bank. This exciting discovery allows us to trial drugs directly on the cells that are diseased and have been affected by a neurological disease. To carry out this technique the post-mortem delay must be minimal and the areas where the cells remain alive in the brain must be removed and processed quickly to get optimal cell growth. These brain cell cultures hold great promise for understanding how diseases of the brain affect individual cells and will allow many new therapies to be trialled.
Genetic studies on Alzheimer’s disease brain tissue
The genetic basis for Alzheimer’s disease causation is a modest one and only in approximately 15% of cases is there an identifiable genetic contribution to the disease. In some forms of dementia there is a far higher contribution such as in fronto-temproal dementia. Nevertheless, it is important to study the genetics as there may be combinations of genes that contribute to the disease that are not currently known. We are interested in studying novel candidate genes that may improve or worsen the symptoms of Alzheimer’s disease and there are new candidates emerging on a regular basis that are of interest to Alzheimer’s disease. In addition, in order to study the effects of specific gene expression on human brain cells in culture, we undertake studies involving knocking genes out or expressing them at high levels in cultured human brain cells. We use the cultured human brain cells to test the effects of individual genes on the cultured stem cells.
Drug discovery for Alzheimer’s disease
We have teamed up with a group of medicinal chemists at the Auckland University who are making potential drugs by using novel chemistry techniques. We are then able to screen them for toxicity and for efficacy in cell cultures including on human Parkinson’s disease cells grown from the brain post-mortem. The classification of the drugs and the targets they work on are diverse and the hope is that one or more of these drugs may one day become useful for slowing the progression of the disease.
For emergencies call 111 or visit your nearest hospital
For general inquiries:
+64 9 923 6072 – Mrs Marika Eszes, Brain Bank Manager
At time of death:
+64 21 287 8476 – Professor Maurice Curtis, Co-Director
The Neurological Foundation Human Brain Bank
Centre for Brain Research
The University of Auckland
Private Bag 92019