A toxic protein produced in the liver is carried through the bloodstream and into the brain. Once there it causes cell damage, inflammation, and memory loss.
Researchers say the finding is exciting because it offers the potential for new Alzheimer's disease prevention and treatment strategies.
The accumulation of the toxic protein beta amyloid is a hallmark feature of Alzheimer's disease. But this protein is found in the blood and other organs as well as the brain.
In a study published in 2019, scientists found that blood levels of amyloid in cognitively healthy people accurately predicted amyloid burden in the brain.
Another study found blood measures could identify patients who would go on to develop Alzheimer’s with a high degree of accuracy.
These studies suggest amyloid damage could originate from other areas of the body and travel to the brain through the bloodstream.
Blood Supplies Brain Cell-Damaging Material
In previous award-winning research, scientists from Curtin University showed that in humans, beta amyloid is not only made in the brain but is carried by molecules made in the liver, molecules called triglyceride-rich lipoproteins (TRL).If TRLs are able to cross through the blood brain barrier, they could be responsible for causing Alzheimer’s disease. But this is difficult to demonstrate because the brain also produces its own beta amyloid, so the researchers had to devise a method to distinguish between the two.
To do this they genetically engineered mice to produce human beta amyloid only in the liver. As in humans they saw this protein being transported in the blood by the same lipoproteins. But the key observation was its passage into the brain.
As a result, the mice developed neurodegeneration, brain atrophy, inflammation, and blood vessel dysfunction. The mice also performed poorly on learning and memory tests.
In their paper, published in the journal Plos Biology in September, the researchers say that their findings are consistent with the proposition put forth by another research group that the liver, not the brain, is the origin of toxic beta amyloid deposits that damage the brain. This could help explain why scientists have found that not everyone with beta amyloid deposits in the brain will go on to develop Alzheimer's disease. Perhaps the beta amyloid produced by the brain isn't damaging to brain cells like the beta amyloid produced by the liver.
Diet and Exercise Can Help
Researchers believe some problem in TRL-amyloid metabolism “may be sufficient to potentially cause Alzheimer’s disease.”They add, “Evidence that the metabolism of TRL-amyloid is a significant risk factor for Alzheimer’s provides new opportunities to consider prevention prospects through diet [and] lifestyle.”
The researchers didn’t expand on what these opportunities are, but presumably they involve eating a diet containing high quality fats, avoiding processed and trans fats, and enjoying sufficient exercise to clear away excess blood fats. They also suggest drugs targeting dysfunction in lipid metabolism, such as cholesterol-lowering drugs, may have a place.
Senior research scientist John Mamo agreed, saying, “Our research shows that these toxic protein deposits that form in the brains of people living with Alzheimer’s disease most likely leak into the brain from fat carrying particles in blood, called lipoproteins.
“This ‘blood-to-brain pathway’ is significant because if we can manage the levels in the blood of lipoprotein-amyloid and prevent their leakage into the brain, this opens up potential new treatments to prevent Alzheimer’s disease and slow memory loss.”
