A new study has found that the neurons in the brain can alter their genetic make-up unlike other cells of the body which remain constant. This genetic modification could be the basis for altered protein formation and deposits. This can lead to several neurodegenerative conditions including Alzheimer’s disease, explain the researchers. The study was published in the latest issue of the journal Nature. Neurologists from world over have hailed this latest study as landmark in the understanding of this progressively debilitating disease. The history of this finding goes back to the 1970s when researchers had found that certain cells of the brain are capable of shuffling and editing their DNA. This was called somatic recombination which was initially seen in the immune cells and then later in the brain. Researchers led by neuroscientist Jerold Chun of the Sanford Burnham Prebys Medical Discovery Institute in San Diego, California looked at donated brains from deceased elderly individuals 6 of whom were healthy at the time of death and seven of whom had noninherited form of Alzheimer’s disease. They looked at the different versions of genes found in these neurons.
These genes all code for the amyloid precursor protein (APP). When altered this gene stimulates the production of amyloid protein that forms deposits or plaques within the brain in patients with Alzheimer’s disease. They had evidence that there were multiple copies of this gene among those with the disease leading to excess production of the protein and its deposits. Somatic recombination was the reason behind this change. They found that neurons in affected brains carry thousands of variants of the APP gene. Some of these variants had a single nucleotide alteration while others had huge chunks of DNA with knitted up or clotted up sections of DNA. Compared to healthy individuals those with Alzheimer’s had six times the variants of the APP gene. They noted that 11 mutations were seen in the rare form of inherited Alzheimer’s disease. Those with no Alzheimer’s did not have these mutations. According to Dr. Chun explained: “Rather than having one constant blueprint that stays with us throughout life, neurons have the ability to change that blueprint. This ability can be the reason behind cognitive development, memory and learning but can also be the reason behind neurodegenerative diseases”.
This team started his specific research a couple of years ago. Already in 2015 they published a work about the “mosaicism” of APP gene inside neurons of a single human brain with Alzheimer disease, characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. Cortical nuclei displayed large variability with average DNA content increases of ~8% over non-diseased controls that were unrelated to trisomy 21. The team believes this somatic or genetic reshuffling could be due to an enzyme with reverse transcriptase (RVT) activity, similar to HIV virus. This enzyme can make copies of DNA from RNA molecules; a variant arises when the enzyme makes RNA copies of the APP gene and a DNA copy from this RNA molecule. This is against the usual (the DNA from the RNA) and thus the copy made is imperfect. This new version of the DNA is different from the original explained Chun and codes for a different APP. Reverse transcriptase enzyme can be blocked by drugs used against HIV infection. This means that these anti-HIV drugs could also help patients with Alzheimer’s disease said Chun.
The team is also looking at the possibility of this mechanism causing other brain diseases such as Parkinson’s disease. The research, anyway, is in its nascent stage and according to the researchers more work needs to be done for confirmation.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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