Genetic ‘hotspots’ that speed up and slow down brain aging could provide new targets for Alzheimer’s drugs


Researchers from a USC-led consortium have discovered 15 “hotspots” in the genome that either accelerate brain aging or slow it down—a finding that is associated with Alzheimer’s disease and other degenerative brain disorders. New drug may provide target to counteract developmental delay. ,

The research appears online today Nature Neuroscience.

“The big game-changer here is discovering locations on the chromosome that accelerate or slow brain aging in populations around the world. These could quickly become new drug targets,” said Paul Thompson of the USC, of ​​the study. Lead author and co-founder and director of the NIGMA Consortium, said, “Through our AI4AD (Artificial Intelligence for Alzheimer’s Disease) initiative, we also have a genome-guided drug repurchase program to target these and discover new and existing drugs. Which helps us age better.”

ENIGMA is the USC-based working group exploring a vast trove of brain data and has published some of the largest neuroimaging studies on schizophrenia, major depression, bipolar disorder, epilepsy, Parkinson’s disease and even HIV infection. have done.

To search for hotspots, or genomic loci, more than 200 ENIGMA-member scientists from around the world looked for people whose brains had been scanned twice with MRI. The scans provided a measure of how fast their brains were gaining or losing tissue in areas that control memory, emotion and analytical thinking.

One lakh markers screened

After calculating brain tissue change rates in 15,000 people of all ages, the researchers examined a million markers in their genomes to locate 15 genomic loci — specific, physical locations of genes on a chromosome, or other DNA sequences — which were accelerating brain tissue changes.

Thompson said these loci include some well-known Alzheimer’s risk genes, such as APOE, and some novel ones. The researchers also found overlap with genes associated with depression, schizophrenia and cognitive functioning.

Co-author Neda Jahanshad, associate professor of neurology at USC’s Keck School of Medicine, said, “Some of these genetic variants affect the rate of growth of brain structures in childhood, while others affect the rate of loss of brain tissue in old age. They affect.” , “Different parts of the brain have specific genes associated with their rate of change.”

Thompson said, “You can see that APOE – the well-known Alzheimer’s gene – adversely affects certain structures of the brain – the hippocampus and the amygdala – which also makes sense because they are the brain regions most vulnerable to Alzheimer’s. And it seems to speed up tissue loss there. Specifically.”

ENIGMA also has international projects studying childhood brain disorders – from Tourette’s syndrome and autism to epilepsy. Researchers said the new list of genes that slow or accelerate brain development in children provides new leads for further development of these disorders as well.

about this study

In addition to Thompson and Jahanshad, other USC scientists involved in the study included Sophia Thomopoulos, Joanna Bright, Leila Nabulsi, Linda Ding and Alyssa Zhu, all from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute. For a complete list of authors, see published study.

The study was supported with funding from the National Institutes of Health including the National Institute of Aging (U01AG068057, R01AG058854, R01AG059874), the National Institute of Mental Health (R01MH117601), the National Institute of Biomedical Imaging and Bioengineering (P41). and Zenith Grant (ZEN-20-644609) from the Alzheimer’s Association.

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Material provided by University of Southern California, Original written by Leigh Hooper. Note: Content can be edited for style and length.

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