pattismith
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This article was published a week ago
"A major new study on Alzheimer's disease provides previously unknown evidence of how the brain-robbing illness may originate.
Moreover, it proposes that certain HIV drugs called reverse transcriptase inhibitors could immediately be repurposed for Alzheimer's patients.
Led by scientists from Sanford Burnham Prebys Medical Discovery Institute in San Diego, the study finds that, as long suspected, Alzheimer's is a genetic disease. But in nearly all cases, it's not inherited. Rather, it arises during a patient's lifetime by genetic rearrangements in neurons. Sequences of DNA are copied, altered and inserted back into the genome.
The genetic rearranging isn't random mutation, but a process that recombines DNA into different patterns. This reshuffling creates a mosaic of slightly differing cells. The immune system uses a similar process to make antibodies, but nothing like it has been seen in the human brain.
Reverse transcriptase inhibitors might also ward off Alzheimer's in those with Down syndrome, who develop Alzheimer's as they age, the study said.
The study was published Wednesday in the journal Nature.etc"
originale study here:
Somatic APP gene recombination in Alzheimer’s disease and normal neurons
Abstract
The diversity and complexity of the human brain are widely assumed to be encoded within a constant genome. Somatic gene recombination, which changes germline DNA sequences to increase molecular diversity, could theoretically alter this code but has not been documented in the brain, to our knowledge. Here we describe recombination of the Alzheimer’s disease-related gene APP, which encodes amyloid precursor protein, in human neurons, occurring mosaically as thousands of variant ‘genomic cDNAs’ (gencDNAs). gencDNAs lacked introns and ranged from full-length cDNA copies of expressed, brain-specific RNA splice variants to myriad smaller forms that contained intra-exonic junctions, insertions, deletions, and/or single nucleotide variations. DNA in situ hybridization identified gencDNAs within single neurons that were distinct from wild-type loci and absent from non-neuronal cells. Mechanistic studies supported neuronal ‘retro-insertion’ of RNA to produce gencDNAs; this process involved transcription, DNA breaks, reverse transcriptase activity, and age. Neurons from individuals with sporadic Alzheimer’s disease showed increased gencDNA diversity, including eleven mutations known to be associated with familial Alzheimer’s disease that were absent from healthy neurons. Neuronal gene recombination may allow ‘recording’ of neural activity for selective ‘playback’ of preferred gene variants whose expression bypasses splicing; this has implications for cellular diversity, learning and memory, plasticity, and diseases of the human brain.
"A major new study on Alzheimer's disease provides previously unknown evidence of how the brain-robbing illness may originate.
Moreover, it proposes that certain HIV drugs called reverse transcriptase inhibitors could immediately be repurposed for Alzheimer's patients.
Led by scientists from Sanford Burnham Prebys Medical Discovery Institute in San Diego, the study finds that, as long suspected, Alzheimer's is a genetic disease. But in nearly all cases, it's not inherited. Rather, it arises during a patient's lifetime by genetic rearrangements in neurons. Sequences of DNA are copied, altered and inserted back into the genome.
The genetic rearranging isn't random mutation, but a process that recombines DNA into different patterns. This reshuffling creates a mosaic of slightly differing cells. The immune system uses a similar process to make antibodies, but nothing like it has been seen in the human brain.
Reverse transcriptase inhibitors might also ward off Alzheimer's in those with Down syndrome, who develop Alzheimer's as they age, the study said.
The study was published Wednesday in the journal Nature.etc"
originale study here:
Somatic APP gene recombination in Alzheimer’s disease and normal neurons
Abstract
The diversity and complexity of the human brain are widely assumed to be encoded within a constant genome. Somatic gene recombination, which changes germline DNA sequences to increase molecular diversity, could theoretically alter this code but has not been documented in the brain, to our knowledge. Here we describe recombination of the Alzheimer’s disease-related gene APP, which encodes amyloid precursor protein, in human neurons, occurring mosaically as thousands of variant ‘genomic cDNAs’ (gencDNAs). gencDNAs lacked introns and ranged from full-length cDNA copies of expressed, brain-specific RNA splice variants to myriad smaller forms that contained intra-exonic junctions, insertions, deletions, and/or single nucleotide variations. DNA in situ hybridization identified gencDNAs within single neurons that were distinct from wild-type loci and absent from non-neuronal cells. Mechanistic studies supported neuronal ‘retro-insertion’ of RNA to produce gencDNAs; this process involved transcription, DNA breaks, reverse transcriptase activity, and age. Neurons from individuals with sporadic Alzheimer’s disease showed increased gencDNA diversity, including eleven mutations known to be associated with familial Alzheimer’s disease that were absent from healthy neurons. Neuronal gene recombination may allow ‘recording’ of neural activity for selective ‘playback’ of preferred gene variants whose expression bypasses splicing; this has implications for cellular diversity, learning and memory, plasticity, and diseases of the human brain.