The same genetic risk factors that make some people more vulnerable to high cholesterol may raise Alzheimer’s risks, too, a new study suggests.
With the causes of Alzheimer’s still unknown, scientists at the Washington University, St Louis, and the University of California, San Francisco are conducting the largest DNA study to date in search of pre-programmed risk factors.
We had already known that one gene linked to Alzheimer’s risks codes for a molecule involved in the movement of cholesterol through the body.
The link between cholesterol and Alzheimer’s may be even stronger than previously thought, however.
In the new genetic analysis, scientists discovered that a small group genes are linked to elevated risks for both Alzheimer’s and heart disease.
In addition to the APOE4 gene (pictured) that we know raises heart disease and Alzheimer’s risks, another nine DNA links between cholesterol and dementia have been discovererd
The prevalence of Alzheimer’s disease is only expected to climb, steeply, as the American population ages and medicine continues to extend lifespans.
But longer lives mean more diseases of old age, including dementia and heart disease.
The development of these diseases may be partly predicted by our genes before we’re even born – and by some of the same genes, no less.
A variant of the APOE4 gene, for example is currently one of the indicators of Alzheimer’s risks that we know of.
This variant of APOE4 has been linked to a four-fold increase in risk for Alzheimer’s disease.
Frustratingly, however, the gene variant is also found in healthy people, so it’s far from a perfect predictor of the disease.
‘The nature of a risk variant is that it’s present in some healthy people, but we see a greater prevalence of it in people with disease,’ explains study co-author and Washington University, St Louis psychiatrist.
It isn’t entirely clear how this segment of DNA influences the brain and its functioning. But we do know how it relates to cardiovascular disease.
APOE4, when it is functioning properly, provides a recipe for a particular protein. That protein links up with fats (or lipids) to form lipoproteins. These molecules help to make sure that fats travel through the bloodstream as they should.
These water-soluble lipoproteins are crucial to making sure that ‘good’ cholesterol from fatty acids gets transported to tissues that soak them up for energy and that ‘bad’ cholesterol is rerouted back to the liver.
If bad cholesterol is not correctly navigated back to the liver, it can instead build up in the blood vessels, constricting the flow of blood through them.
This of course puts greater strain the heart which has to pump all he harder to push enough blood through the narrow passageways.
So those with a faulty variant of the gene are more likely to have higher cholesterol.
As it turns out, this may also have something to do with the accumulation of amyloid protein plaques in the brain, which scientists suspect is among the underlying causes of Alzheimer’s.
By combing through DNA from 1.5 million people, the new study’s authors found 90 DNA segments that they could link to people with heart disease risk factors, including diabetes, high cholesterol and high BMI.
Six of these seemed strongly predictive of both heart disease and Alzheimer’s – further suggesting the connection between the transportation of lipids through the bloodstream and plaque formation in the blood.
‘This study has done two things to really solidify this connection’ between genes related to lipids and risks of heart disease and Alzheimer’s, Dr Karch says.
‘This shows that there are multiple genes that are contributing to risks for these cardiovascular traits that contribute to heart disease as well as Alzheimer’s risks,’ says Dr Karch.
‘It also functionally falls into this pathway related to lipid metabolism and lipids in general [in both heart disease and Alzheimer’s].’
And her study found these traits in a large sample, contributing to the weight the findings carry.
‘Lipids are really important for normal health of cells of all types in your brain,’ says Dr Karch.
‘They play an important role in the ability of your cells to transport these disease-causing proteins as well as the ability of the cell to degrade these disease-causing proteins.’
The team also discovered that some gene variants related to the immune system raised Alzheimer’s risks.
Dr Karch says that this doesn’t mean everyone should rush off to get genetic tests.
‘It’s challenging to say now that a genetic test will give you a clear answer as to your certainty of developing Alzheimer’s disease,’ she says.
‘But when we think about holistic health, treatments and preventative health can be crucial to taking care of of cardiovascular health, and [doing that] early may have benefits for cognitive health later in life.’
In theory, a low-fat diet would mean there would be less cholesterol that needed to be cleared out of the bloodstream, somewhat mitigating the importance of the genetically determined ability to transport cholesterol out of the blood.
If that theory plays out in our biology, then keeping cholesterol low might also help reduce the risk of amyloid proteins building up in the brain and reduce the risk of Alzheimer’s.
That also suggests that drugs meant to control cholesterol may be useful tools for reducing Alzheimer’s risks.