A young Kiwi researcher is unravelling what could prove a crucial link between insulin and the most common form of dementia.
Alzheimer's disease is projected to affect 70,000 Kiwis by 2031 - yet present treatments don't do enough to slow the progression of the debilitating disease.
For decades, neuroscientists have been gathering evidence from the brains of patients to try to understand the disease, and there are today several well-supported theories.
While it's sometimes unclear how these theories fit together, all could partly explain what causes the massive brain cell death seen in the disease.
A project by University of Auckland researcher Catherine Webb focused on a relatively recent theory called the "insulin dysregulation hypothesis".
"Most people have heard of the hormone insulin because of its involvement in diabetes, but it is also very important in promoting the survival and function of neurons," she said.
"Certain clues, such as the fact that diabetic patients are more likely to develop Alzheimers disease, and the fact that insulin improves the memory of experimental animals with it, show that insulin is somehow involved in the disease."
Therefore, she said, the insulin receptor could offer an interesting drug target.
Her Science Scholar research project, supervised by Auckland University brain researchers Associate Professor Maurice Curtis and Dr Helen Murray, searched for insulin receptors in the hippocampus, the sea-horse shaped part of the brain that forms new memories and which is most damaged in dementia.
"This is important because the location of receptors says a lot about their function," she said.
"In what part of the brain, on what cell type, and where in the cell a receptor is located; all of this influences the function of the receptor and how a drug could be used to target it."
Using samples from recently-deceased donors to the New Zealand Neurological Foundation Douglas Human Brain Bank, Webb compared the hippocampus of normal brains and those affected by Alzheimer's.
"Very thin slices from these blocks were stained by joining fluorescently coloured molecules to the proteins we are interested in with animal antibodies," she said.
"When we look at these sections under a microscope, the proteins we stained for appear in bright colours against a dark background."
"We stained for insulin receptors, cell nuclei - so we knew where the cells were - and a protein that is only found in a certain type of neuron, so we knew what kind of brain cells we were looking at.
"In this way we could see where and how much the insulin receptor is expressed in the hippocampus, and whether the location or amount changes with Alzheimer's."
The biggest challenge was that the insulin receptor antibody had never been used on brain tissue before.
That meant Webb and her colleagues had to work out the optimal conditions for getting the antibody to bind.
"There were a lot of things to test here, including pH, temperature, concentration, and whether to break up the tissue with enzymes or not, so this optimisation process took up most of my project."
Ultimately, her work helped fill what could be an important gap in understanding how the disease works - and how to beat it.
"A lot of evidence shows that insulin has effects on brain cells which may be related to Alzheimer's disease, but no-one has previously characterised the location of insulin receptors in post-mortem brain tissue," she said.
"In the long term, this kind of work is needed to know whether it is worth making a drug to target the insulin receptor in some way to treat Alzheimer's disease."