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A study published in the journal JAMA Neurology suggests that low density lipoprotein (LDL) cholesterol levels, sometimes called "bad" cholesterol, play a causal role in the development of Alzheimer's disease.
Structure of lipoproteins (chylomicron): ApoA, ApoB, ApoC and ApoE – apolipoproteins; T – triacylglycerol, ceo – cholesterol ester, green phospholipids. Image Credit: Xvaz Quez / CC BY-SA 3.0.
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. About 10% of Alzheimer's cases are early.
Previous studies have shown that the disease is largely based on genetics, which means that it will probably be inherited if a parent is infected with it.
It is known that four specific gene variants – called APP, PSEN1, PSEN2 and APOE E4 – are linked to early-onset Alzheimer's disease. APOE E4 is known to increase circulating cholesterol levels, especially LDL.
"The big question is whether there is a causal link between blood cholesterol levels and the risk of Alzheimer's disease," said Dr. Thomas Wingo, a neurologist at the Atlanta Veterans Affairs Medical Center and at the Faculty of Medicine at Emory University.
To test whether early-onset Alzheimer's disease is related to cholesterol and to identify the genetic variants that might underlie this possible badociation, Dr. Wingo and his colleagues sequenced specific genomic regions of 2,125 people, 654 of whom had Alzheimer's at early onset and 1,471 controls.
The researchers also tested 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.
They also tested APP, PSEN1 and PSEN2. About 3% of early Alzheimer's cases have at least one of these known risk factors for early Alzheimer's.
After testing blood samples, scientists found that participants with elevated LDL levels were more likely to have early-onset Alzheimer's disease than patients with lower cholesterol levels.
This was true even after the team had controlled cases with the APOE mutation, which means that cholesterol could be an independent risk factor for the disease, regardless of whether the problematic variant of the APOE gene is present or not.
The authors of the study found no badociation between high density lipoprotein (HDL) cholesterol levels and the early onset of Alzheimer's disease, and only a very slight badociation between disease and stroke rates. triglycerides.
They 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 discovery suggests a direct link between the rare mutation of APOB and the risk of Alzheimer's disease," said Dr. Wingo and his co-authors.
"However, APOE or APOB has not explained in detail the link between LDL-C level and early onset of Alzheimer's disease, suggesting that other genes and mechanisms also increase the risk of illness. "
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Thomas S. Wingo et al. Association of early-stage Alzheimer's disease with high levels of cholesterol in low density lipoproteins and rare variants of APOB genetic coding. JAMA Neurol, published online May 28, 2019; doi: 10.1001 / jamaneurol.2019.0648
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