High LDL level linked to Alzheimer's disease at an early stage

Researchers at Atlanta Veterans Affairs Medical Center and Emory University have discovered a link between high LDL cholesterol levels and early-stage Alzheimer's disease. The findings could help doctors understand how the disease develops and what the possible causes are, including genetic variation.

According to Dr. Thomas Wingo, lead author of the study, the results show that LDL cholesterol levels could play a causal role in the development of Alzheimer's disease.

The results appear in the May 28, 2019 edition of JAMA Neurology.

"The big question is whether there is a causal link between cholesterol levels in the blood and the risk of Alzheimer's disease," Wingo says. "Existing data is troublesome on this point.One of the interpretations of our current data is that LDL cholesterol plays a causal role.If this is the case, we may need to revisit the cholesterol goals in the LDCs. to reduce the risk of Alzheimer's.Our work is now centered on the test of the existence of a causal link ".

Wingo is a neurologist and researcher at Atlanta VA and at Emory University.

High cholesterol levels have been associated with an increased risk of Alzheimer's disease later in life. This risk may be due to genetic factors related to cholesterol. Previous research has shown that a major risk factor for Alzheimer's disease is a specific mutation of a gene called APOE. This is the most important genetic risk factor known for Alzheimer's disease. This variant of APOE, called APOE E4, is known to increase circulating cholesterol levels, especially low density lipoproteins (LDL). This type of cholesterol is sometimes called "bad cholesterol" because high levels of LDL can cause cholesterol buildup in the arteries.

Although late-onset Alzheimer's disease – the usual form of the disease – appears to be related to cholesterol, little research has been conducted on a possible link between cholesterol levels and the risk of disease. Alzheimer's early onset.

Alzheimer's disease at an early stage is a relatively rare form of the disease. The disease is considered "early" when it appears before the age of 65 years. About 10% of Alzheimer's cases are early. Previous research has shown that the disease is largely based on genetics, which means that it will probably be inherited if a parent is infected with it.

Three specific gene variants (called APP, PSEN1 and PSEN2) are known to be linked to Alzheimer's disease at an early stage. APOE E4 is also a risk factor in this form of disease. These gene variants account for about 10% of early-onset Alzheimer's disease cases, meaning that 90% of cases are unexplained.

To test whether early-onset Alzheimer's disease is related to cholesterol and to identify the genetic variants that may underlie this possible association, the researchers sequenced specific genomic regions of 2,125 people, of which 654 were Alzheimer's disease patients at early onset and 1,471 were controls. They also analyzed blood samples from 267 participants to measure the amount of LDL cholesterol.

They discovered that APOE E4 accounted for about 10% of early-onset Alzheimer's disease cases, which is similar to estimates for late-onset Alzheimer's disease. The researchers also tested APP, PSEN1 and PSEN2. About 3% of early-onset Alzheimer's cases had at least one of these known risk factors for early-onset Alzheimer's.

After testing blood samples, the researchers found that participants with elevated LDL levels were more likely to contract early-stage Alzheimer's disease than patients with lower cholesterol levels. This was true even after the researchers controlled APOE mutation cases, which meant that cholesterol could be an independent risk factor for the disease, regardless of whether the problematic variant of the APOE gene was present or not.

Researchers have not found a link between HDL (high-density lipoprotein) and early Alzheimer's disease levels, and only a very slight association between disease and triglyceride levels.

The researchers also discovered a new genetic risk factor for Alzheimer's disease at an early stage. Early onset Alzheimer's cases were more common in participants with a rare variant of a gene called APOB. This gene encodes a protein involved in the metabolism of lipids, or fats, including cholesterol. The finding suggests a direct link between the rare APOB mutation and the risk of Alzheimer's disease, according to the researchers. However, the link between APOE and APOB does not fully explain the link between LDL-C and early onset of Alzheimer's disease, suggesting that other genes and mechanisms also increase the risk of illness.

Although the study highlights the possible risk factors for early-stage Alzheimer's disease, the researchers say there is a need for further research to fully explain the link between disease and cholesterol. The relative scarcity of Alzheimer's disease at an early stage is a challenge in finding enough samples to be able to perform important genetic studies on the disease, they say.

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