麻豆传媒

Proteins taken from the brains of Alzheimer鈥檚 patients and injected into the brains of genetically engineered mice trigger Alzheimer鈥檚-like lesions in the mouse brains, researchers report.

The findings suggest that the malformed protein clumps associated with Alzheimer鈥檚 disease can 鈥渟eed鈥� themselves in a way reminiscent of the missfolded proteins in prion diseases such as 鈥渕ad cow鈥� disease.

The exact causes of Alzheimer鈥檚 remain a mystery, but it appears that beta-amyloid proteins contribute to the formation of disruptive plaques in the brain. The neurological damage accumulates over years, causing loss of memory, language and other crucial mental skills.

Experts studying how beta amyloid might promote plaque formation have speculated that this might happen in a process similar to that in prion diseases.

Infectious agents

Prion illnesses, such as mad cow disease, are special in that proteins apparently act as the infectious agents, rather than genetic material or a microorganism. In laboratory tests, animals that receive prion proteins develop brain plaques and eventually die as a result.

Previous experiments have shown that injections of brain extracts from Alzheimer鈥檚 patients can trigger brain plaque formation in marmoset monkeys and mice.

But it has not been clear whether the beta-amyloid proteins themselves are responsible for this effect, or some other component of the brain tissue, says Lary Walker at Emory University in Atlanta, Georgia, US.

To investigate this, Walker鈥檚 team used 鈥淎PP23 mice鈥� 鈥� genetically engineered to carry the human gene with a mutation that causes the animals to develop plaques in old age.

Seed hunting

When the young APP23 mice received brain extracts from either humans who had died with Alzheimer鈥檚 disease, or from older APP23 mice, the young mice developed brain plaques within weeks instead of the usual year.

Next, the team took brain extracts from old APP23 mice and exposed them to molecules that specifically bind and disable beta-amyloid proteins. When these treated extracts were injected into the brains of young mice, they did not cause the formation of plaques.

鈥淔or the first time we show that the likely seed is beta amyloid itself,鈥� says Walker.

He notes that there is no evidence to suggest that beta amyloid alone can accelerate Alzheimer鈥檚-like plaques in mice that are not genetically predisposed to the illness.

Walker adds that the evidence from the new experiment should encourage scientists to find out which forms of beta amyloid might promote plaque formation most aggressively in humans.

Journal reference: Science (DOI: 10.1126/science.1131864)