APOE4 opens the way to the brain
The risk factor breaks through the blood-brain barrier
Marina Astvatsaturyan, Echo of Moscow
The most noticeable distinguishing features of Alzheimer's disease for researchers are clusters of improperly folded beta-amyloid and tau proteins deposited in the brain. But recently, there is more and more data indicating changes in the blood-brain barrier as early signs of this neurodegenerative disease.
The blood-brain barrier, a physiological barrier between the circulatory and central nervous systems, protects the brain from foreign microbes and substances circulating in the blood. The degree of damage to the blood-brain barrier correlates with the degree of cognitive impairment experienced by patients, but what exactly causes "holes" in this barrier remained unknown. In the latest issue of the journal Nature, Axel Montagne with colleagues from The University of Southern California presented evidence that the main risk factor for Alzheimer's disease, apolipoprotein E4, is associated with a violation of the integrity of the blood–brain barrier (Montagne et al., APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline).
The apolipoprotein E gene – it is called APOE – encodes the ApoE protein, which plays an important role in lipid metabolism. There are three main variants of this gene: APOE2, APOE3 and APOE4. The latter option significantly increases the risk of developing Alzheimer's disease. In people with one copy of this variant inherited from one of the parents, the probability of getting sick is increased fourfold, and in those who got the APOE4 variant from both parents, that is, carriers of two copies of this gene, the risk of developing Alzheimer's disease increases by 15 times.
As noted USC News, in cognitively preserved people, but at the same time carriers of APOE4, plasma proteins were found in the cerebrospinal fluid washing the brain and spinal cord, and subsequently these people develop Alzheimer's disease. Plasma proteins presumably penetrated the blood-brain barrier, therefore, the integrity of the barrier was lost even before the decline in mental abilities.
Axel Montagnier and colleagues investigated the permeability of the blood-brain barrier in people with normal cognitive abilities and with a moderate decrease preceding the manifestation of the disease by MRI with dynamic contrast enhancement. The subjects were grouped according to the status of the APOE gene. It turned out that in cognitively healthy people with one or two copies of APOE4, the barrier is broken in two areas of the brain responsible for memory and mental activity, these are the hippocampus and the gyrus of the hippocampus. In the case of moderate cognitive impairment in APOE4 carriers, the "holes" in the barrier are more pronounced.
Portal "Eternal youth" http://vechnayamolodost.ru