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

Date:
April 5, 2022
Source:
University of Southern California
Summary:
Researchers have discovered 15 'hotspots' in the genome that either speed up brain aging or slow it down -- a finding that could provide new drug targets to resist Alzheimer's disease and other degenerative brain disorders, as well as developmental delays.
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Researchers from a USC-led consortium have discovered 15 "hotspots" in the genome that either speed up brain aging or slow it down -- a finding that could provide new drug targets to resist Alzheimer's disease and other degenerative brain disorders, as well as developmental delays.

The research appears online today in Nature Neuroscience.

"The big game-changer here is discovering locations on the chromosome that speed up or slow down brain aging in worldwide populations. These can quickly become new drug targets," said Paul Thompson of USC, a lead author on the study and the co-founder and director of the ENIGMA Consortium. "Through our AI4AD (Artificial Intelligence for Alzheimer's Disease) initiative we even have a genome-guided drug repurposing program to target these and find new and existing drugs that help us age better."

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

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

A million markers screened

After computing brain tissue change rates in 15,000 people of all ages, researchers screened a million markers in their genomes to detect 15 genomic loci -- specific, physical locations of genes or other DNA sequences on a chromosome -- that were speeding up brain tissue changes.

These loci included some well-known Alzheimer's risk genes, such as APOE, and some novel ones, Thompson said. The researchers also found overlap with genes involved with depression, schizophrenia and cognitive functioning.

"Some of these genetic variants affect the growth rates of brain substructures in childhood, while others affect the speed of brain tissue loss in older adulthood," said co-author Neda Jahanshad, an associate professor of neurology at the Keck School of Medicine of USC. "The different parts of the brain have specific genes associated with their rates of change."

Thompson added, "You can see that APOE -- the famous Alzheimer's gene -- hits a couple of brain structures adversely -- the hippocampus and amygdala -- which also makes sense as they are the brain regions most vulnerable to Alzheimer's and it seems to speed tissue loss there specifically."

ENIGMA also has international projects studying childhood brain disorders -- from Tourette syndrome and autism to epilepsy. The new list of genes that slow down or speed up brain growth in children provides new leads to pursue in these disorders as well, the researchers said.

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 full list of authors, see the published study.

The study was supported with funding from the National Institutes of Health, including the National Institute on Aging (U01AG068057, R01AG058854, R01AG059874), the National Institute of Mental Health (R01MH117601), the National Institute of Biomedical Imaging and Bioengineering (P41 EB015922), and a Zenith Grant (ZEN-20-644609) from the Alzheimer's Association.


Story Source:

Materials provided by University of Southern California. Original written by Leigh Hopper. Note: Content may be edited for style and length.


Journal Reference:

  1. Rachel M. Brouwer, Marieke Klein, Katrina L. Grasby, Hugo G. Schnack, Neda Jahanshad, Jalmar Teeuw, Sophia I. Thomopoulos, Emma Sprooten, Carol E. Franz, Nitin Gogtay, William S. Kremen, Matthew S. Panizzon, Loes M. Olde Loohuis, Christopher D. Whelan, Moji Aghajani, Clara Alloza, Dag Alnæs, Eric Artiges, Rosa Ayesa-Arriola, Gareth J. Barker, Mark E. Bastin, Elisabet Blok, Erlend Bøen, Isabella A. Breukelaar, Joanna K. Bright, Elizabeth E. L. Buimer, Robin Bülow, Dara M. Cannon, Simone Ciufolini, Nicolas A. Crossley, Christienne G. Damatac, Paola Dazzan, Casper L. de Mol, Sonja M. C. de Zwarte, Sylvane Desrivières, Covadonga M. Díaz-Caneja, Nhat Trung Doan, Katharina Dohm, Juliane H. Fröhner, Janik Goltermann, Antoine Grigis, Dominik Grotegerd, Laura K. M. Han, Mathew A. Harris, Catharina A. Hartman, Sarah J. Heany, Walter Heindel, Dirk J. Heslenfeld, Sarah Hohmann, Bernd Ittermann, Philip R. Jansen, Joost Janssen, Tianye Jia, Jiyang Jiang, Christiane Jockwitz, Temmuz Karali, Daniel Keeser, Martijn G. J. C. Koevoets, Rhoshel K. Lenroot, Berend Malchow, René C. W. Mandl, Vicente Medel, Susanne Meinert, Catherine A. Morgan, Thomas W. Mühleisen, Leila Nabulsi, Nils Opel, Víctor Ortiz-García de la Foz, Bronwyn J. Overs, Marie-Laure Paillère Martinot, Ronny Redlich, Tiago Reis Marques, Jonathan Repple, Gloria Roberts, Gennady V. Roshchupkin, Nikita Setiaman, Elena Shumskaya, Frederike Stein, Gustavo Sudre, Shun Takahashi, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Aad van der Lugt, Neeltje E. M. van Haren, Joanna M. Wardlaw, Wei Wen, Henk-Jan Westeneng, Katharina Wittfeld, Alyssa H. Zhu, Andre Zugman, Nicola J. Armstrong, Gaia Bonfiglio, Janita Bralten, Shareefa Dalvie, Gail Davies, Marta Di Forti, Linda Ding, Gary Donohoe, Andreas J. Forstner, Javier Gonzalez-Peñas, Joao P. O. F. T. Guimaraes, Georg Homuth, Jouke-Jan Hottenga, Maria J. Knol, John B. J. Kwok, Stephanie Le Hellard, Karen A. Mather, Yuri Milaneschi, Derek W. Morris, Markus M. Nöthen, Sergi Papiol, Marcella Rietschel, Marcos L. Santoro, Vidar M. Steen, Jason L. Stein, Fabian Streit, Rick M. Tankard, Alexander Teumer, Dennis van ‘t Ent, Dennis van der Meer, Kristel R. van Eijk, Evangelos Vassos, Javier Vázquez-Bourgon, Stephanie H. Witt, Rüdiger Brühl, Dimitri Papadopoulos Orfanos, Tomáš Paus, Sabina Millenet, Hieab H. H. Adams, Ingrid Agartz, David Ames, Katrin Amunts, Ole A. Andreassen, Celso Arango, Tobias Banaschewski, Bernhard T. Baune, Sintia I. Belangero, Arun L. W. Bokde, Dorret I. Boomsma, Rodrigo A. Bressan, Henry Brodaty, Jan K. Buitelaar, Wiepke Cahn, Svenja Caspers, Sven Cichon, Benedicto Crespo-Facorro, Simon R. Cox, Udo Dannlowski, Torbjørn Elvsåshagen, Thomas Espeseth, Peter G. Falkai, Simon E. Fisher, Herta Flor, Janice M. Fullerton, Hugh Garavan, Penny A. Gowland, Hans J. Grabe, Tim Hahn, Andreas Heinz, Manon Hillegers, Jacqueline Hoare, Pieter J. Hoekstra, Mohammad A. Ikram, Andrea P. Jackowski, Andreas Jansen, Erik G. Jönsson, Rene S. Kahn, Tilo Kircher, Mayuresh S. Korgaonkar, Axel Krug, Herve Lemaitre, Ulrik F. Malt, Jean-Luc Martinot, Colm McDonald, Philip B. Mitchell, Ryan L. Muetzel, Robin M. Murray, Frauke Nees, Igor Nenadić, Jaap Oosterlaan, Roel A. Ophoff, Pedro M. Pan, Brenda W. J. H. Penninx, Luise Poustka, Perminder S. Sachdev, Giovanni A. Salum, Peter R. Schofield, Gunter Schumann, Philip Shaw, Kang Sim, Michael N. Smolka, Dan J. Stein, Julian N. Trollor, Leonard H. van den Berg, Jan H. Veldink, Henrik Walter, Lars T. Westlye, Robert Whelan, Tonya White, Margaret J. Wright, Sarah E. Medland, Barbara Franke, Paul M. Thompson, Hilleke E. Hulshoff Pol. Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nature Neuroscience, 2022; DOI: 10.1038/s41593-022-01042-4

Cite This Page:

University of Southern California. "Genetic 'hotspots' that speed up and slow down brain aging could provide new targets for Alzheimer's drugs." ScienceDaily. ScienceDaily, 5 April 2022. <www.sciencedaily.com/releases/2022/04/220405171804.htm>.
University of Southern California. (2022, April 5). Genetic 'hotspots' that speed up and slow down brain aging could provide new targets for Alzheimer's drugs. ScienceDaily. Retrieved April 22, 2024 from www.sciencedaily.com/releases/2022/04/220405171804.htm
University of Southern California. "Genetic 'hotspots' that speed up and slow down brain aging could provide new targets for Alzheimer's drugs." ScienceDaily. www.sciencedaily.com/releases/2022/04/220405171804.htm (accessed April 22, 2024).

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