麻豆传媒

The transmission of abnormal proteins that form tangles in cells may explain how Alzheimer鈥檚 spreads throughout a patient鈥檚 brain, research shows.

鈥淲e鈥檝e shown how it probably progresses within an individual person,鈥� says co-leader of the research team, of the Laboratory of Molecular Biology in Cambridge, UK.

Goedert and his colleagues demonstrated the key role played by the 鈥渢au鈥� protein tangles by injecting the brains of healthy mice with brain material from mice which make the abnormal form of the protein.

By the end of the experiment, the tangles had spread beyond the sites where they had originally been injected to many distant parts of the brain.

Drug hope

Because the healthy mice were incapable of making the tau tangles themselves, the only explanation is that the tangles somehow spread or dispersed to neighbouring tissue from the site where they were injected. 鈥淭hey never usually develop these tangles,鈥� says Goedert.

The researchers hope to use the same system to identify which forms of the tau protein spread the symptoms, and how to block them with drugs.

Normal tau proteins are vital for managing the transport of materials within brain and other cells. They stabilise tiny filaments called microtubules, which serve almost like railway lines along which material is transported. But in Alzheimer鈥檚 disease, the tau proteins somehow become abnormal 鈥� perhaps because of inflammation 鈥� and form clumps, or tangles, which kill brain cells.

Typical progression

Now, it鈥檚 clear that they somehow spread between cells. Goedert says that the results help to explain what Alzheimer鈥檚 researchers had long known about progression of the disease in patients. Usually, it starts in a region called the transentorhinal cortex, a kind of junction for memory impulses. But people with damage in this area seldom if ever suffer any symptoms.

Only when the disease progresses 鈥� firstly to the hippocampus, the brain鈥檚 memory centre, then the cerebral cortex, the site where memories are consolidated 鈥� do symptoms begin to appear and worsen.

Goedert and his colleagues hope that if they can find a way of diagnosing and blocking the disease when it has only reached the transentorhinal cortex, they can stop it progressing to the other vital memory areas.

They are confident that the dual-mice model they have developed will help them identify which types of tau tangles spread the symptoms most efficiently, how they form in the first place, and how they can be blocked.

of the University of Virginia says that the findings fit perfectly with recent results published in this month鈥檚 showing in lab tissue culture that tau tangles can penetrate and 鈥渋nfect鈥� cells from the outside. It therefore seems quite possible that tau pathology spreads from cell to cell within the body too, says Bloom.

鈥楴o infection risk鈥�

Goedert cautions that the experiment in mice only shows how tau tangles spread within an infected brain, and shouldn鈥檛 be taken to mean that such tangles can spread from person to person. 鈥淭here鈥檚 absolutely no evidence to suggest that Alzheimer鈥檚 disease is infectious,鈥� he says.

He says, though, there are parallels between the capacity of the tau tangles to spread from cell to cell, and the well-known ability of abnormal prion proteins to spread disorders like mad cow disease in cattle and its human counterpart, variant Creutzfeldt-Jakob disease (vCJD) in humans.

However, unlike prion proteins, there鈥檚 no evidence the tau tangles can survive outside the body and thereby contaminate surgical instruments or donated blood.

鈥淭here is some commonality, but it shouldn鈥檛 imply they are infectious in the same ways,鈥� says Goedert. 鈥淲hat we鈥檝e investigated is how it spreads within brains.鈥�

One of the most successful drugs yet against Alzheimer鈥檚 disease is one which neutralises the tau tangles. Rember, developed by spun out from the University of Aberdeen, dissolves the tangles, and in a trial published last July slowed disease progression by 81 per cent in one year compared with control patients.

Journal reference: (DOI: 10.1038/ncb1901)