In a new study, researchers found that high levels of LDL cholesterol (‘bad’ cholesterol) in the body may play a causal role in the development of Alzheimer’s disease.
The finding could help doctors understand how the disease develops and find possible causes and treatments.
The research was conducted by a team from the Atlanta Veterans Affairs Medical Center and Emory University.
Increased cholesterol levels have been linked to increased risk of Alzheimer’s later in life. This risk may be due to genetic factors tied to cholesterol.
Previous research has shown that a major risk factor for Alzheimer’s disease is a specific mutation in a gene referred to as APOE.
It is the largest known single genetic risk factor for Alzheimer’s disease.
This APOE variant, called APOE E4, is known to raise levels of circulating cholesterol, particularly low-density lipoprotein (LDL).
This type of cholesterol leads to a build-up of cholesterol in the arteries.
Studies have shown that whether there is a causal link between cholesterol levels in the blood and Alzheimer’s disease risk is a big question.
But the existing data have been murky on this point.
In the current study, the team focused on early-onset Alzheimer’s, a relatively rare form of the condition.
The disease is considered “early-onset” when it appears before age 65. About 10% of all Alzheimer’s cases are early-onset.
Three specific gene variants (dubbed APP, PSEN1, and PSEN2) are known to be related to early-onset Alzheimer’s disease. APOE E4 is also a risk factor in this form of the disease.
In the study, the team examined specific genomic regions of 2,125 people, 654 of whom had early-onset Alzheimer’s and 1,471 of whom were controls.
They also tested blood samples of 267 participants to measure the amount of LDL cholesterol.
They found that APOE E4 explained about 10% of early-onset Alzheimer’s, which is similar to estimates in late-onset Alzheimer’s disease.
The tests for APP, PSEN1, and PSEN2 showed that about 3% of early-onset Alzheimer’s cases had at least one of these mutations.
They also found that participants with increased LDL levels were more likely to have early-onset Alzheimer’s disease, compared with patients with lower cholesterol levels.
LDL cholesterol could be an independent risk factor for the disease, regardless of whether the problematic APOE gene variant is present.
The team explains that one interpretation of our current data is that LDL cholesterol does play a causal role in the development of Alzheimer’s disease.
If that is the case, it is possible to control LDC cholesterol to help reduce Alzheimer’s risk.
Their current work is focused on testing the causal link.
The lead author of the study is Dr. Thomas Wingo, a neurologist, and researcher with the Atlanta VA and Emory University.
The study is published in JAMA Neurology.
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