New cause of dementia uncovered as scientists link ‘innocent’ peptide to devastating condition

Scientists may have discovered a new cause of Alzheimer’s disease, which could hold the key to a new treatment.

In a new commentary, a team at the University of California, Santa Cruz, argued that decades of dementia research has focused on the wrong protein.

For years, and in hundreds of trials, scientists have focused on treatments targeting the protein amyloid beta — a hallmark of Alzheimer’s that can form clumps in the brain that disrupt communication between nerve cells.

But in their work, the California team argues that a lesser-known ‘cousin’ peptide of amyloid beta may be behind the disease.

The protein, known as P3 or amyloid alpha, is made at the same time as amyloid beta and had previously been considered harmless.

But, after reviewing existing research and carrying out three studies of their own, the team said it could be toxic to brain cells and form the same damaging protein clumps that have been linked to the disease.

Dr Jevgenij Raskatov, the chemist who led the piece, said: ‘The P3 peptide is, most likely, not the innocent bystander it was commonly thought to be.

‘There’s still more research to be done, but this could turn Alzheimer’s research on its head.’

He added: ‘P3 is a distinct aggregating peptide that is itself potentially neurotoxic and may be contributing to Alzheimer’s disease.’

More than 7 million Americans have Alzheimer disease and cases are expected to nearly double in the US in the next 25 years, rising to nearly 13 million by 2050.

The disease is debilitating and gradually robs sufferers of the ability to live independently, speak and recognize familiar faces.

Despite spending billions on clinical trials and new drugs targeting amyloid beta proteins, scientists have had little success in treating the disease.

Many experts are now exploring other theories for its causes, including suggestions that it may be linked to damaged blood vessels or  complications in the liver.

In their commentary published in the journal ChemBioChem, however, the scientists argue that it is still likely that a protein build-up in the brain is behind the disease.

Amyloid beta is formed when a much larger protein, called the amyloid precursor protein, is broken up by the enzymes beta-secretase and then y-secretase.

But this same process also forms the P3 protein as an offshoot.

As well as reviewing dozens of studies, the team has also now published three major manuscripts investigating the protein, which show it is at least as capable as amyloid beta of forming amyloid deposits — and maybe producing them more rapidly.

Despite the work, however, Raskatov said other scientists remained unaware of their advances. 

In his review, he found at least four scientific studies published in reputable journals that cited his own team’s work as evidence that P3 was not toxic, the opposite of what they had found. 

He said: ‘We remain in the dark on how this sort of grand confusion may have come about. Clearly, there is more work ahead of us.’ 

Current treatments targeting amyloid beta have had limited results to date, slowing the disease’s progression but not reversing it.

Raskatov added: ‘Progress has been extremely slow, and the current state of the art in Alzheimer’s therapy leaves much to be desired. We need fundamentally new approaches to the problem.’

The team’s work was reviewed by Dr David Teplow, an emeritus professor of neurology at the University of California, Los Angeles, who said it shifted his understanding.

He said: ‘This re-evaluation has far-reaching consequences for both basic science and clinical research into the causes and treatment of Alzheimer’s disease.’