Alzheimer's culprit may be 'innocent'
Wrong culprit Amyloid proteins may have been wrongfully accused as the culprits behind Alzheimer's disease, new research in mice suggests.
Two studies - one Australian, one from the US - have examined the role amyloid proteins play in the brain with one study suggesting that far from being a destructive force, amyloid may in fact play a protective role.
In a study from Stanford University, treating multiple-sclerosis mice with a key component of notorious amyloid proteins such as beta-amyloid, prion and tau not only reduced brain inflammation but also reversed the paralysis associated with the disease.
The results, published in Science Translation Medicine, follow earlier research that used the amyloid proteins to successfully treat mice with multiple sclerosis, despite the fact that amyloid had originally been thought to play a negative role in the disease.
Lead author and professor of neurology at Stanford University Professor Lawrence Steinman says the findings add weight to other studies that show in animals born without the genes that generate amyloid, their disease is much worse.
"We were so fixated on the idea that amyloid is bad for the brain that if one goes back and looks at the old literature and the new literature, one finds there's a lot of publications where people have ignored these kinds of experiments in humans where, for instance, lower levels of amyloid are associated with earlier dementia," says Lawrence.
Instead, Lawrence suggests that amyloid proteins may be the brain's way of soaking up harmful molecules that are part of the inflammatory process.
"I like to think of them as a surgical sponge in that, because of their chaperone activities and their sticky surfaces, they're very good at the site of damage to sponge up dangerous and harmful molecules that are at the site of disease," he says.
Plaques appear later
Meanwhile, Australian researchers have found evidence in a mouse model of Alzheimer's disease that the characteristic amyloid plaques actually appear much later in the disease, long after the development of cognitive symptoms such as memory loss.
"The conclusion of our study, taken together with other studies is that behavioural decline, neuronal cell death and inflammatory cell activation precede plaque deposition, providing a strong indication that neurodegenerative processes are occurring independent of amyloid-beta protein," the researchers write in PLoS One.
Lead scientist, Dr Bryce Vissel says a new theory of disease - that emphasises the role of inflammation rather than the role of amyloid protein - is emerging in the field of Alzheimer's research.
"The hypothesis is that the inflammation in the brain, potentially driven by external inflammation in some cases, is driving brain damage, impairment and neurodegeneration," says Vissel, head of the neurodegenerative research lab at the Garvan Institute of Medical Research.
Anti-amyloid treatments may work in those who are genetically predisposed to overproduce amyloid proteins, Vissel says.
However the recent failure of numerous clinical trials of anti-amyloid therapies suggests in the majority of individuals with this devastating disease, other strategies may be needed.
"Our study suggests that we will need to treat disease earlier and possibly with approaches other than targeting plaque load."