Alzheimer research breakthrough

Researchers from the University of Sydney's Alzheimer's and Parkinson's Disease Laboratory have achieved a breakthrough by finding the causes of Alzheimer's disease at a cellular level and thereby identifying a potential therapy as a result.

The study led by Professor Jürgen Götz and Dr Lars Ittner, based at the University's Brain and Mind Research Institute (BMRI), was published in the international scientific journal Cell.

The researchers have discovered how a protein called TAU affects and mediates the toxicity of amyloid-b, which together with TAU causes the symptoms of Alzheimer's disease.

Professor Götz said this breakthrough has implications for how the disease develops and how it may be treated.

"More than 250,000 Australians are currently diagnosed with dementia, with numbers reaching epidemic proportions. Of all diseases with a memory loss, Alzheimer's is the most prevalent, predicted to affect one in 85 people globally by 2050," he said.

"A handful of approved drugs provide, if at all, only very modest symptomatic relief, without curing the disease. Therefore, to develop effective treatments, it is absolutely necessary that the basic mechanisms underlying these disorders be understood. This was our challenge."

The brain of all Alzheimer's patients is characterised by two types of insoluble deposits: amyloid-b plaques and neurofibrillary tangles, the latter formed by the protein TAU.

Dr Ittner said they focused on the relationship between the two, which produced a finding that challenges the accepted research paradigm.

"TAU was always thought to be a protein exclusively localised to the axons of neurons, but at the same time amyloid-b exerts its toxic effects at the dendritic site of the synapse, which is at the other end of the neuron," he said.

"The more data we obtained the clearer it became to us that TAU must have an as yet unrecognised function in the dendrite, so finally we had to break with the dogma of TAU being an exclusively axonal protein."

The researchers found that TAU is essential for the positioning of yet another protein, the kinase FYN, at the dendritic site of the synapse, which then renders the neuron vulnerable to amyloid-b.

"By genetically deleting TAU or introducing a non-functional variant of TAU, we found we could prevent the development of symptoms in mouse models of Alzheimer's disease.

"These mice showed normal survival and their memory appeared to be perfectly fine."

In the second part of the study, Professor Götz and Dr Ittner explored the potential of their discovery for a treatment of Alzheimer's disease.

"We translated our findings into a novel therapeutic approach by using a small peptide that mimics the effects of removing TAU from the synapse, and we were thrilled to see that this not only fully prevented the pathology in our Alzheimer's disease models but cleared their memory deficits," Dr Ittner said.

"Although there is still a long way to go, we believe we may have found a way of treating Alzheimer's disease," adds Professor Götz.