While
we still do not know exactly what causes the development of Alzheimer's
disease, specialists have been hard at work trying to identify the most salient
risk factors. New research has now identified a new player when it comes to
Alzheimer's risk: the liver.
New
research highlights the liver's potential role in raising the risk of
Alzheimer's.
This
week, at the yearly Alzheimer's Association
International Conference — held in Chicago, IL — researchers led by
Dr. Mitchel A. Kling, an associate professor of psychiatry at the University of
Pennsylvania in Philadelphia, have presented the intriguing findings of their latest study.
They
observed that Alzheimer's disease risk
is associated with reduced levels of plasmalogens, a type of phospholipid
produced in the liver. They play key roles in maintaining the health of brain
cells.
From
the liver, plasmalogens are carried to the brain and other organs through the
blood. Levels of these phospholipids can be measured through specialized tests
that have been devised by Dr. Kling in collaboration with colleagues from the
Alzheimer's Disease Metabolomics Consortium at Duke University in Durham, NC.
The
researchers identified three indices — assessing the ratios of different
plasmalogens to each other, the ratios of plasmalogens to other lipids, and a
combination of these measurements — that allow them to determine the amount of
plasmalogen as it relates to cognitive functioning.
Specifically,
they were interested in confirming whether decreased plasmalogen levels were
linked with an increased risk of developing various degrees of cognitive
impairment, including: Alzheimer's disease, mild cognitive impairment (MCI), or
significant memory concerns (SMC).
Changes in the liver
influence risk
Dr. Kling and team assessed the levels of several different
plasmalogens, including ones containing specific omega-3 fatty acids:
docosahexaenoic acid (DHA), and eicosapentaenoic acid. They also measured the
levels of one omega-6 fatty acid, and of some nonplasmalogen lipids closely
related to plasmalogens.
The measurements were taken in samples of blood-based bodily
fluids collected from two different groups of study participants.
The first group was made of 1,547 people diagnosed with
Alzheimer's disease, MCI, or SMC, as well as a number of people confirmed to be
cognitively normal. These participants were enrolled in the Alzheimer's Disease
Neuroimaging Initiative.
The second group was made of 112 individuals with Alzheimer's
or MCI, or who were considered cognitively normal. These latter participants
were recruited via the Penn Memory Center.
Dr. Kling and colleagues saw that lower values of the
indices they measured corresponded to a higher risk of developing Alzheimer's,
and a similar association was observed for MCI diagnoses.
Moreover, the scientists also noticed that decreased levels
of certain plasmalogens appeared to be linked with heightened levels of the tau
protein, which is a hallmark of Alzheimer's disease.
"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," notes Dr. Kling.
"This 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."
Dr. Mitchel Kling
"This could lead to the eventual destruction of the
peroxisomes [functional elements within cells] that create plasmalogens which
thus, increases the risk of Alzheimer's."
A 'promising' journey
of discovery
These observations, the team adds, might also explain why
Alzheimer's patients who receive fish oil or supplementary DHA do not show any
improvement of cognitive function.
This may happen because the liver is unable to integrate the
fatty acids into the plasmalogens.
Another intriguing notion is the fact that certain genes
thought to play a role in Alzheimer's disease also regulate the transport and
metabolism of lipids, so researchers are now interested in finding out whether
this has any bearing on the relationship between lipid production and brain
health.
"Our findings provide renewed hope for the creation of
new treatment and prevention approaches for Alzheimer's disease," Dr.
Kling explains. "Moving forward, we're examining the connections between
plasmalogens, other lipids, and cognition, in addition to gene expression in
the liver and the brain."
"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," he adds.
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