HIV and Alzheimer's
The APP gene, responsible for the appearance of toxic beta-amyloid plaques, plays a key role in the pathogenesis of Alzheimer's disease, a neurodegenerative disease that currently affects more than 6 million people in the United States alone.
Scientists from the Sanford Burnham Prebis Institute of Medical Discovery studied samples of brain tissue from patients with Alzheimer's disease. Using modern techniques that allow analyzing both individual cells and their groups, they found that the APP gene undergoes various changes (recombination), which leads to the appearance of new genetic variants in neurons. Due to the fact that these changes occur independently in each cell, a genetic mosaic is formed. Reverse transcription and reinsertion of genetic variants into the original genome are involved in this process, ensuring permanent changes in DNA within each cell.
According to the study, in one hundred percent of cases of Alzheimer's disease, brain tissue samples contained significantly more different variants of the APP gene than in healthy tissue samples.
Among this variety of genetic variants, scientists have identified 11 single-nucleotide substitutions that occur in the rarest hereditary form of the disease. Also, variants most characteristic of classical Alzheimer's disease were found in this genetic mosaic, which additionally links the recombination of genes in neurons with the development of the disease.
The researchers also found that the process of recombination of genes requires the presence of a special enzyme – reverse transcriptase. It is noteworthy that it is due to the work of this enzyme that the human immunodeficiency virus penetrates into cells.
Despite the lack of evidence that HIV or AIDS leads to the development of Alzheimer's disease, scientists suggest that antiretroviral therapy blocking the effect of reverse transcriptase can also stop the recombination process described above and act as a new potential drug for Alzheimer's disease. This hypothesis is also supported by data on the low incidence of Alzheimer's disease among elderly patients with HIV receiving antiretroviral therapy.
The data obtained during this study may also explain why more than 400 clinical trials dedicated to the fight against Alzheimer's disease failed: each study was aimed at suppressing any one specific variant of the APP gene. Now, knowing about recombination and the variety of genetic variants that it generates, it becomes obvious that a different approach is needed to treat Alzheimer's disease.
Article by Lee et al. Somatic APP gene recombination in Alzheimer's disease and normal neurons is published in Nature.
Anastasia Poznyak, portal "Eternal Youth" http://vechnayamolodost.ru / based on EureaAlert: Never-before-seen DNA recombination in the brain linked to Alzheimer's disease.