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WEDNESDAY, May 29, 2019 (HealthDay News) – Another reason to keep cholesterol under control: New research suggests that LDL, or "bad" cholesterol, may play a role in the development of Alzheimer's disease at the early onset.
A rare form of the disease that occurs before the age of 65, early Alzheimer's disease has already been linked to a genetic mutation involved in how the body processes fats and cholesterol . But this mutation represents only a small percentage of cases, noted scientists.
Their new research suggests that "LDL cholesterol levels [also] plays a causal role in the pathogenesis of Alzheimer's disease, "said lead researcher Dr. Thomas Wingo, who is an badistant professor of neurology at the Emory University School of Medicine in Atlanta.
"The big question is whether there is a causal link between cholesterol levels in the blood and the risk of Alzheimer's disease," Wingo said. "Existing data is troublesome on this point.Our current job is to check if there is a causal link."
Early onset Alzheimer's disease is not explained by known gene mutations, added Wingo.
The genetic mutation of APOE, called APOE E4, increases LDL cholesterol levels. High levels of this type of cholesterol can clog the arteries and increase the risk of heart attack and stroke.
Other genetic mutations badociated with early-stage Alzheimer's disease are called APP, PSEN1 and PSEN2.
But all these genetic variants are badociated with only about 10% of all cases of early Alzheimer's disease. That leaves 90% of all early cases of Alzheimer's unexplained, said Wingo.
For the study, he and his colleagues sequenced specific gene areas of more than 2,100 people. Of these, more than 650 have suffered from Alzheimer's disease at an early stage. In addition, over 260 participants saw their cholesterol levels checked.
The researchers found that the APOE E4 mutation accounted for about 10% of early-onset Alzheimer's disease, which is identical to that seen in late-onset Alzheimer's disease.
They also searched for APP, PSEN1 and PSEN2 mutations and found that about 3% of patients with early-onset Alzheimer's disease had at least one of these variants.
The Wingo team also found that participants with elevated LDL cholesterol levels had a higher risk of early-onset Alzheimer's disease compared to those with lower LDL levels.
LDL cholesterol levels remained high even after accounting for APOE mutations. Thus, cholesterol could be an independent risk factor for Alzheimer's disease at an early stage, said Wingo, although the study did not show that high LDL cholesterol levels were at the origin of Alzheimer's disease at an early stage.
No links have been found between Alzheimer's disease and HDL cholesterol ("good"). A slight badociation has however been observed with triglyceride levels.
A link between LDL cholesterol and early Alzheimer's disease has not been fully explained by APOE nor by an even rarer mutation of the gene called APOB, suggesting that factors including other genes could increase the risk, said Wingo.
"If there is a causal link between Alzheimer's disease and cholesterol, it might be necessary to revisit LDL cholesterol goals to help reduce the risk of Alzheimer's disease." ", did he declare.
Dr. Sam Gandy, director of the Center for Cognitive Health of Mount Sinai and NFL Neurological Care in New York, said the results are credible and likely to be replicated in the coming months.
This discovery confirms the long-held suspicions that cholesterol is one of the major players in Alzheimer's disease, he said.
This is particularly noteworthy as it can have major implications for treatment, said Gandy, who was not involved in the study. "It's a very exciting counterpoint to the loss of enthusiasm for direct targeting of amyloid plaques in the brain," he said.
For years, it was thought that the accumulation of protein plaques in the brain could be a possible cause of Alzheimer's disease, but recent trials of drugs aimed at reducing amyloid levels have showed little effect on the disease.
The report was published online on May 28 in the journal JAMA Neurology.
More information
Visit the Alzheimer's Association to find out more about Alzheimer's disease.
SOURCES: Thomas Wingo, M.D., Assistant Professor, Neurology, Emory University School of Medicine, Atlanta; Sam Gandy, MD, Ph.D., professor of neurology and psychiatry at the Icahn School of Medicine in New York and director of the Mount Sinai Center for Cognitive Health and NFL Neurological Care in New York; May 29, 2019, JAMA Neurologyonline
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