Cell Biology: Alzheimer's Disease

By Tim Groenendyk

With Australia’s population of people aged over 65 set to double by the year 2050, the number of people suffering from Alzheimer’s Disease will similarly increase. Claire Goldsbury’s Alzheimer’s Cell Biology Laboratory at the Brain and Mind Research Institute attempts to understand the disorder at the most fundamental level.

Claire Goldsbury and the Alzheimer

"My lab’s hypothesis is that the cofilin aggregates form first and that recruits the tau aggregates. We’re looking for some evidence of that – the research in that area is quite new.” Claire Goldsbury, head of the Alzheimer’s Cell Biology Laboratory

“If you’ve got a hangover and you have an energy drink it might make you feel better for about half an hour but it’s not actually going to cure the hangover,” said Dr Claire Goldsbury, describing an analogy she believes fits the climate of Alzheimer’s pharmaceutical treatment.

“It gives you a little blip of activity, and that’s pretty much what all the Alzheimer drugs on the market do.

“They’re just treating the symptoms not the cause. They’re not altering the progression of the disease.”

Goldsbury, head of the Alzheimer’s Cell Biology Laboratory at the BMRI, started her research career in medicine with a PhD on diabetes - focussing on amyloid protein deposits in the pancreas.

These deposits are present in other diseases, such as prion disease, mad cow disease and Alzheimer’s disease.

Using the techniques she learnt from this research Goldsbury applied this knowledge of protein aggregates to Alzheimer’s disease research, examining the cellular aspects of the disorder in the brain’s cytoskeleton.

The cytoskeleton is a protein scaffold, or skeleton, necessary for all cells in the body to maintain their structure, shape and functions.

“It’s also important for movement, and transport processes,” explained Goldsbury.

“But what happens in Alzheimer’s is that the skeleton somehow breaks down and you end up with cells that have accumulations of cytoskeletal proteins in the wrong place. And this happens along this transport route.

“The hypothesis is that these accumulations then interfere with the functions of the neuron. They stop the transport, they stop synapses working – and synapses are, basically, what makes memory.

“When that breaks down that’s what causes the disease.”
Her Laboratory is attempting to ascertain how these cytoskeletal inclusions - which are visible in the brain cells of deceased people with the disorder - are generated.

“What we’re doing is pretty basic; growing cells in petri dishes, and then artificially trying to make inclusions form in a normal cell.”

By making a normal cell behave like an Alzheimer’s cell, Goldsbury hopes they will understand the process of how Alzheimer’s occurs.

There’s strong evidence suggesting defective tau proteins cause Alzheimer’s disease, but Goldsbury’s lab believes cofilin proteins may play a major part as well.

“Tau protein aggregates are found in all Alzheimer’s Disease patients and they’re thought to be responsible for the dysfunction of the neurons.

“But my lab’s hypothesis or idea is that the cofilin aggregates form first and that recruits the tau aggregates.

“We’re looking for some evidence of that – the research in that area is quite new,.”

So that poses another question: if these proteins are responsible for causing Alzheimer’s Disease, what causes these aggregations in the first place?

The answer may be found in the cell’s energy centre – mitochondria – and the brain, a very energy hungry organ, experiences energy deficiency with ageing. Goldsbury took the idea to her lab’s cell cultures.

“We found that when we inhibited the mitochondria, reducing their output of energy, we could induce the generation of these cofilin aggregates.

“These aggregates would then seem to recruit phosphorylated tau or tau-like proteins.

“It showed that cells that are energetically compromised could be triggered to go along a pathway where they start to form Alzheimer-like aggregates.

“But whether that’s occurring in a brain is another question really.”
Until that question is answered what can we do prevent the disease?

“Social, mental and physical activity, and maintaining a good diet.

“More and more it’s becoming evident that Alzheimer’s and dementia are associated with ageing – a bit like cardiovascular disease, diabetes and obesity are. The two diseases may be linked in some way.

“So having the same risk factors, keeping your heart and body healthy is also going to help your brain.”