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New research has shown a link between high LDL cholesterol levels and early Alzheimer's disease.
The findings could help doctors understand how the disease is evolving and what are the possible causes, including genetic variation, according to researchers at Atlanta Veterans Affairs Medical Center and Emory University.
According to Dr. Thomas Wingo, neurologist and researcher at Atlanta VA and Emory University, the results show that LDL cholesterol levels could play a determining role in the development of Alzheimer's disease.
"The big question is whether there is a causal link between blood cholesterol levels and the risk of Alzheimer's disease," said Wingo, lead author of the study. "Existing data has been troubled 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 revise the goals of LDL cholesterol to reduce the risk of Alzheimer's disease. Our job now is to check if there is a causal link. "
High cholesterol has been badociated with an increased risk of Alzheimer's disease later in life. The researchers believe that 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 in a gene called APOE. It 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 build up in the arteries, the researchers said.
While late Alzheimer's disease – the most common 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 early Alzheimer's disease, according to the reports. researchers.
Early-stage Alzheimer's is a relatively rare form of the disease, occurring before the age of 65. About 10% of all Alzheimer's cases are at an early stage. Previous research has shown that the disease is largely based on genetics, which means that it will likely be inherited if a parent is infected, according to the scientists.
Three variants of specific genes – APP, PSEN1 and PSEN2 – are known to be linked to early-onset Alzheimer's disease. APOE E4 is also a risk factor in this form of the disease. These gene variants account for only about 10% of cases of early-onset Alzheimer's disease, which means that 90% of cases are unexplained, the researchers noted.
To test whether early-onset Alzheimer's disease is related to cholesterol and to identify the genetic variants that might underlie this possible badociation, the researchers sequenced specific genomic regions of 2,125 people, of whom 654 had the disease. Early onset Alzheimer's and 1,471 others. They also badyzed blood samples from 267 participants to measure the amount of LDL cholesterol.
They found that APOE E4 accounted for about 10% of early Alzheimer's cases, which is similar to estimates of late Alzheimer's disease.
The researchers also tested APP, PSEN1 and PSEN2. The study found that about 3% of early Alzheimer's cases had at least one of these known risk factors for early Alzheimer's.
After testing blood samples, the researchers found that participants with high LDL levels were more likely to have early-stage Alzheimer's disease, compared to 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, the researchers explained.
The researchers found no link between high density lipoprotein (HDL) cholesterol levels and the early onset of Alzheimer's disease, and only a very slight badociation 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 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 LDL-C and early-onset Alzheimer's has not been fully explained by APOE or APOB, suggesting that other genes and mechanisms also increase the risk of disease, the authors said. researchers.
The researchers say more research is needed to fully explain the link between disease and cholesterol. The relative scarcity of early-stage Alzheimer's disease is a challenge in finding enough samples to conduct major genetic studies of the disease, they add.
The study was published in JAMA Neurology.
Source: Veterans Affairs
Photo: Drs. Thomas Wingo and Aliza Wingo (in the foreground) conduct a laboratory in Atlanta and Emory University dedicated to understanding the genetic underpinnings of Alzheimer's disease and psychological well-being and resilience. Credit: Lisa Pessin.
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