They discover the connection between Alzheimer’s and cholesterol

An investigation led by the Hospital of Sant Pau (Barcelona) has identified a key alteration in it Brain cholesterol transportation and their collection by neurons in patients with Alzheimer’s and presence of apoe4 genea finding that could help explain the origin of the disease.

The results of the study, published in Journal of Lipid Research, They point out that lipoproteins of the cerebrospinal fluid of patients with this neurodegenerative pathology have a reduced capacity to supply cholesterol to neurons. “We know for a long time that people with the APOE4 variant, especially in form homozygousthey have a very high risk of developing Alzheimer’s, but so far it was not well known why. Our study indicates that one of the factors that could contribute is that neuronsin the presence of this variant, they capture worse cholesterol that comes to them by cerebrospinal fluid“The researcher has detailed Mireia Tondoof the Sant Pau Research Institute.

The “vital” role of cholesterol

Colesterol has a vital role for the proper functioning of neurons, intervenes in the Membrane formationin the synaptic transmission and in the Myelin production. However, the brain does not receive this blood molecule, as it occurs in other organs, since the Hematoencephalic barrier prevents it. “All necessary cholesterol is produced locally,” explained Dr. Tondo, which specifies that later “is stored in specific lipoproteic particles that transport it from glial cells to neurons” and, in case this process fails, “the neuron may not receive the structural and functional resources it needs.”

The researchers analyzed samples of cerebrospinal fluid 10 patients with Alzheimer’s and 10 people without illnessfrom cohort Sant Pau Initiative on Neurodegeneration (Spin). From these, they evaluated two stages of cerebral lipid transport; On the one hand, the ability of Astrocytes to yield cholesterol to the cerebrospinal fluid; And, on the other, the ability of neurons to capture That cholesterol. The results showed that the release by astrocytes was similar In all participants, but that neuronal collection was clearly Committed In patients with Alzheimer’s.

Given this result, the team wanted to understand if this defect could be related to genetics, so they created recombinant lipoproteic nanoparticlesidentical to each other but with APOE3 either APOE4and detected that those containing APOE4 transferred cholesterol much less efficient. “This made us think that this variant could have a direct role in the observed dysfunction,” Tondo said.

On the other hand, the research team carried out a detailed proteomic analysis of the lipoproteins of the cerebrospinal fluid. They identified 239 Proteins associated with these particles, of which 27 were altered In patients with Alzheimer’s, but none of these differences directly affected proteins related to the cholesterol metabolism. “This finding indicates that the lipoproteic system is much more complex than we thought, and that there may be other mechanisms related to inflammationthe Cellular adhesion wave Protein degradation which can also influence the progression of the disease, “added the researcher.

New research line

In conclusion, researchers have highlighted the importance of finding on the disturbance In the cholesterol capture system by neurons, since it opens a line of research related to cerebral lipid metabolism. However, they insist that you have to be prudent With the results, “this study does not allow to affirm that the cholesterol deficit is the direct cause of the disease, but it could be one of the factors that contribute to the neuronal damage“said Dr. Tondo.

The group already works on a new study to see if this mechanism for collection of neuronal cholesterol is also altered in people with Down syndrome, A collective with genetic risk of developing Alzheimer’s. “This could help us understand if there are common mechanisms and if improving lipid metabolism could be a way to delay neurodegeneration“The expert ended.

The investigation has been possible thanks to the collaboration between the lipid metabolism group and the Sant Pau memory unit, in addition to the participation of researchers in the area of ​​neurodegenerative diseases of the Network Bionedical Research Center (Ciberned), the National Cardiovascular Research Center (CNIC), the area CIBER cardiovascular diseases (Cibercv) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2).