Azlheimer’s disease linked to HIV-like biochemical reactions involving APP gene

In opposition to a view of constant genome shaping human brain, specific biochemical changes on a level of individual neurons may play an essential role in diseases.

Gene APP is an important point in the current model of Alzheimer’s disease emergence. Its mutations and duplications cause at least some cases of the disease.

In addition to previously known, inherited disruptions of APP gene and acquired trisomy in Down syndrome (3 copies of APP), it was found that specific changes in brain regions and individual neuron cells should also participate in the disease etiology.

The study proposes that reverse transcriptase enzyme inserts copies of APP into genomes of neuronal cells. Created and detected variants were named as gencDNAs – genomic DNAs. Their number and diversity rises with age and is strictly correlated with Alzheimer’s disease development.

Reverse transcriptase is also used by HIV and its activity is suppressed during anti-retroviral therapy. Interestingly, individuals with ongoing therapy have lower rates of Alzheimer’s disease development. This connection suggests that anti-retrotranscriptase therapy may be an efficient approach in Alzheimer’s disease prevention.

Apart from diseases, discovered mechanism may be used by neuron cells to “record” information in their genome. Probably APP gene is not the only one gene retrotranscribed in brain cells, and reverse transcriptase activity has some, physiologically-important functions.

More: “Somatic APP gene recombination in Alzheimer’s disease and normal neurons”, M-H. Lee et al., 2018, doi:10.1038/s41586-018-0718-6.