Gene recombination sheds light on Alzheimer's failures, suggests HIV drugs could help

A new understanding of amyloid precursor protein (APP) variants from researchers at Sanford Burnham Prebys Medical Discovery Institute and University of California San Diego could help explain why Alzheimer's disease candidates targeting the amyloid pathway have failed in the clinic and offer a new therapeutic approach via HIV drugs.

In a paper published in Nature Wednesday, the researchers identified the first known instance of somatic gene recombination in the brain using in situ hybridization. RNA retro-insertion, in which complementary DNA (cDNA) copied from RNA via reverse transcription is inserted into the genome, produced thousands of genomic cDNA variants of APP in neurons. Neurons from sporadic AD patients had a higher diversity of variants than from individuals without the disease, including 11 mutations that had previously been linked to familial AD...