Scientists have presented new research pointing to the liver as a potential culprit in the onset of Alzheimer's disease. Presented at the Alzheimer's Association International Conference, the research suggests that a compound produced in the liver can confer neurocognitive protections, and when the liver cannot effectively produce those compounds then cognitive deficits can result in the brain.
Molecules called plasmalogens were the primary focus of the new research. These are a class of lipids generated in the liver, and certain types have been found to be critical for effective synaptic function in the brain. The study set out to measure whether reduced levels of several specific types of plasmalogens corresponded with an increased risk of Alzheimer's or mild cognitive decline.
Over 1,500 human subjects were examined, split into three categories: those clinically diagnosed with Alzheimer's disease, those with clinically diagnosed mild cognitive impairment, or those healthy and cognitively normal. The results showed statistically significant differences in plasmalogen levels between all three groups with lower levels associated with higher rates of Alzheimer's or cognitive decline.
"This research shows that an age-related deficiency of plasmalogens could lead to an increased risk of Alzheimer's disease, because the liver cannot make enough of them," says Mitchel Kling, one of the researchers on the project.
The study isn't the first to implicate the liver as playing a role in the onset of Alzheimer's disease. A compelling study from 2011 found that one of the primary genes suspected in production of the pathogenic amyloid beta protein is mostly expressed in the liver. This study hypothesized that the proteins that are thought to be responsible for many cognitive deficits seen in Alzheimer's actually originate in the liver and then travel to the brain via the bloodstream.
Another study, similarly focused on the liver, found that an enzyme the organ produces generates fundamental neuroprotective effects, and when a person's liver isn't effectively producing it brain metabolism can suffer. This particular study was also examining a liver-generated lipid, much like the recent work.
Perhaps the most interesting implication suggested by this growing body of research is that dietary effects on the liver may play a role in the subsequent development of Alzheimer's and cognitive impairment. A recent study does back up this possible hypothesis, finding an association between non-alcoholic fatty liver disease and increased risk of Alzheimer's.
"[The new research] highlights a potential relationship between conditions such as obesity and diabetes and Alzheimer's – as the liver has to work harder to break down fatty acids over time," explains Kling. "This could lead to the eventual destruction of the peroxisomes that create plasmalogens which thus, increases the risk of Alzheimer's."
It is still early days for much of this research but it offers intriguing pathways suggesting scientists could do well by looking outside of the brain when trying to find new ways to approach and treat Alzheimer's disease.
"Moving forward, we're examining the connections between plasmalogens, other lipids, and cognition, in addition to gene expression in the liver and the brain," says Kling. "While we're in the early stages of discovering how the liver, lipids, and diet are related to Alzheimer's disease and neurodegeneration, it's been promising."
The results of this new study was presented at the recent Alzheimer's Association International Conference (AAIC) 2018 in Chicago.
Source: Penn Medicine News
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