News / 19 September 2018

The mystery of what causes Alzheimer’s disease is a step closer to being solved, thanks to an innovative collaboration between an EMBL Australia scientist and his colleague at the South Australian Health and Medical Research Institute (SAHMRI).

The story began as a serendipitous chat on Alzheimer’s disease between EMBL Australia group leader and computational geneticist Dr Ville-Petteri Mäkinen and a cell biologist from SAHMRI’s Nutrition and Metabolism theme, Dr Tim Sargeant.

Now Dr Mäkinen and his team, Dr Song Gao and Dr Aaron Casey, and Dr Sargeant have revealed a genetic link between Alzheimer’s and the endo-lysosomal system, a critical part of biological recycling machinery that maintains the health of brain cells.

Dr Mäkinen says the endo-lysosomal system acts like a garbage disposal service, removing and recycling damaged material within cells.

“The brains of people with Alzheimer’s and other dementias are riddled with abnormal deposits of molecular waste. We know that the endo-lysosomal system is less efficient in an ageing brain and that failures in the system cause unwanted material to accumulate. But it’s not yet certain if these deposits are a cause or a symptom of cognitive decline, or how the disease progresses at the molecular level.”

“The exciting aspect of our research is that we’ve now found a genetic link between the genes that comprise the endo-lysosomal system and Alzheimer’s risk. Because DNA is set at conception and stays the same, genetic variation may affect disease risk but not vice versa; that’s why the genetic association we observed can be considered causal evidence. This is significant for Alzheimer’s, since we now have a reason to prioritize the endo-lysosomal system as a promising target for further studies and drug development.”

Dr Sargeant says late-onset Alzheimer’s disease has no known treatments that can stop or slow progression, and new ideas are desperately needed as the demographics of world populations are shifting towards old age.

“One of the greatest challenges with Alzheimer’s is the lack of effective treatments, or medications to slow progress or stop progression of symptoms,” Dr Sargeant said.

“This research is an important step in understanding how dysfunction in the brain’s recycling machinery may cause Alzheimer’s disease, and may be the key to unlocking new drug targets, or treatment strategies.”

Alzheimer’s disease is the most common form of dementia, affecting around 70 per cent of dementia sufferers.

Without a significant medical breakthrough, more than 6.4 million Australians will be diagnosed with dementia over the next 40 years, at an estimated cost of more than $1 trillion to the health care system.

The research findings were published in the Oxford Academic journal Brain.

This article was originally published on the SAHMRI website and was republished here with permission.

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