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lab researchers examining genetic links to alzheimer's

High LDL Cholesterol May Contribute to Early-Onset Alzheimer’s

By | May 28th, 2019

A new study published in JAMA Neurology links high levels of “bad” LDL cholesterol with early-onset Alzheimer’s.

According to lead author of the study Dr. Thomas Wingo, the results show that elevated LDL cholesterol levels may play a role in the development of the early-onset Alzheimer’s, independent of other risk factors. The study may have also found a new genetic risk factor for early-onset Alzheimer’s.

Related: Is Cholesterol Behind Alzheimer’s? Here’s What We Know

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Young-onset Alzheimer’s, as it’s also known, is a diagnosis of the disease before the age of 65. It’s considered a relatively rare form of the condition, accounting for 10 percent of all Alzheimer’s cases.

Alzheimer’s Disease, Genes and Cholesterol – What’s the Link?

To test the link between Alzheimer’s and cholesterol, independent of genetic risk factors, the researchers sequenced specific genomic regions of 2,125 people, 654 of whom had early-onset Alzheimer’s and 1,471 healthy people for the control group. They also tested the blood of 267 participants to measure their cholesterol.

The genetic mutation ApoE4 is a known risk factor for Alzheimer’s but only explains 10% of the cases. Three other gene variants – APP, PSEN1 and PSEN2 — are known risk factors for early-onset Alzheimer’s.

Read More: Can You Change the Course of Your Genetic Risk for Alzheimer’s?

In this experiment, the researchers’ results aligned with current data. They found that the genetic mutation ApoE4 explained 10% of the early-onset Alzheimer’s cases. About 3% of participants with early-onset had at least one of the other gene variants (APP, PSEN1, PSEN2).

The blood lipid profiles showed that people with elevated LDL cholesterol levels were more likely to have early-onset Alzheimer’s compared to people with lower cholesterol levels. This was true even after controlling for ApoE4. They did not find a link between “good” HDL cholesterol and early-onset Alzheimer’s, and only a slight association between high triglycerides and young-onset Alzheimer’s.

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LDL cholesterol can lead to the buildup of fatty deposits in the arteries (also known as atherosclerosis), thus narrowing the arteries and increasing the risk for heart attacks and strokes. “Good” HDL cholesterol may help prevent heart attacks by guiding LDL away from the arteries to be processed by the liver.

These new findings validate current health recommendations to stay heart-healthy to lower your risk of dementia.

New Genetic Mutation Identified as Alzheimer’s Risk Factor

The researchers also found that early-onset Alzheimer’s cases were higher in people with a rare gene variant called APOB. This gene encodes a protein that plays a role in the metabolism of lipids, or fats, including cholesterol. This finding suggests a direct link between APOB and Alzheimer’s disease risk.

Still, the researchers point out that all of the early-onset Alzheimer’s cases could not be fully explained by APOE or APOB, suggesting that other genes and mechanisms are also to blame.

Read More: Scientists Discover 3 New Common Genetic Threads Among Alzheimer’s Patients

More research is needed to fully explain the link between cholesterol and Alzheimer’s disease.

[Image Credit: Lisa Pessin]

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