Washington - A group of New England scientists say they have confirmed what Alzheimer’s disease researchers have long theorised but had been unable to prove: the brain-killing illness is caused by the deposit of a protein in the brain, known as beta amyloid, that triggers a devastating series of dementia-causing events.
Scientists at Massachusetts General Hospital also identified an enzyme that plays a key role in the progression of the disease – thereby offering a target for pharmaceutical-makers to develop a drug that would halt the neurodegenerative disease.
Their results were published online in the journal Nature.
The team also arrived at their conclusion using an innovative laboratory culture they dubbed “Alzheimer’s-in-a-dish”. Instead of cultivating single-layer cultures of test cells in two-dimensional liquid-based systems, the team grew multiple-layered cultures of neural stem cells in gelatin-like, three-dimensional models that more closely resemble the brain.
The scientists used the 3D cultures to answer a simple question: does beta amyloid actually cause Alzheimer’s disease?
For some time since Bavarian doctor Alois Alzheimer first identified the condition that bears his name, scientists have known that the distinguishing features of Alzheimer’s disease were the presence of two protein variants: amyloid beta, which forms insoluble plaques, and tau, which creates neurofibrillary tangles.
Scientists have also known that both must be present for the symptoms of Alzheimer’s – cognitive impairment, loss of memory and inability to perform certain motor activities – to appear.
But it wasn’t clear whether beta amyloid caused the tangles as some, beginning at least with George Glenner in the 1980s, hypothesised or whether the two were simply associated with each other.
Rudolph Tanzi, director of the genetics and ageing research unit at Massachusetts General Hospital, said his team’s research offers the first definitive proof that Glenner and others were correct that beta amyloid is the cause.
“The question was, does the amyloid really cause the tangles, because the tangles are what kill the nerve cells? And this is the first proof of concept in a human nerve cell system that it does,” said Tanzi.
Tanzi and Doo Yeon Kim, the paper’s co-author, believed that standard two-dimensional cultures had been inadequate environments for growing cells that thrive in the 3D brain. So the team used a 3D culture with neural stem cells that carried variants in two genes – the amyloid beta precursor and presenilin 1 – that are found in early onset, familial Alzheimer’s.
The approach worked faster and more efficiently even than experiments using animals, he said.
“The brain is a gel. The brain is three pounds of actual, gelatin-like material. So let’s grow them in a gelatin-like material,” he said. “And now two things happen. The neurons can grow in a three-dimensional manner, and when they secrete amyloid beta protein like they do in the brain, it stays around. It gets secreted, but it actually diffuses very slowly through Jello instead of liquid.” – The Washington Post