Cholesterol modulation could be explored in the search for Alzheimer’s therapies
▲ A gene called apolipoprotein E, which is involved in cholesterol metabolism and transport, is linked to disease in the elderly Photo Christine Daniloff / MIT
La Jornada newspaper
Wednesday, September 1, 2021, p. 2
Madrid. New research has found an elevated supply of cholesterol from astrocytes to neurons in the Alzheimer’s brain model, suggesting that modulation of that lipid could be explored in the search for treatment options for this devastating degenerative disease, the authors published. in the journal Stem Cell Reports.
Alzheimer’s, the most common cause of dementia, affects about 24 million people in the world. With very limited treatment options, scientists are looking for ways to better understand the disease.
One of its distinctive features is the appearance of so-called beta-amyloid plaques, clusters of this protein in the brain and which are believed to be toxic to adjacent neurons. The causes of the disease and the formation of these plaques remain largely unknown, but genetic studies have found that a gene called apolipoprotein E (ApoE), which is involved in the metabolism and transport of cholesterol, is related to cholesterol. bad in the elderly. It exists in different versions in people: ApoE2, ApoE3 and ApoE4, but the latter carries a relatively higher risk of developing the condition.
Interestingly, in the brain, it is primarily supporting cells called astrocytes and not neurons that produce the ApoE protein. To find out if the ApoE4 gene in them is related to the disease, Jinsoo Seo and his colleagues at the Daegu Gyeongbuk Institute of Science and Technology in South Korea used human-induced stem cells that carried different versions of the ApoE gene to create neurons. and astrocytes in the laboratory and study their interaction. The researchers discovered that astrocytes carrying the ApoE4 gene, associated with evil, released more cholesterol than those with ApoE3.
The scientists observed that neurons exposed to a higher level of cholesterol had different changes in their cell membranes, the outer layers that normally contain cholesterol.
Furthermore, this high cholesterol content in cell membranes was directly related to the increased production and secretion of beta-amyloid from neurons.
This work illustrates how different versions of the ApoE gene in astrocytes can influence beta-amyloid production in neurons, and how excess cholesterol in ApoE4 astrocytes could promote the formation of plaques of this protein in Alzheimer’s patients. .