Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain

Journal: Molecular Psychiatry

Published: 2020-07-10

DOI: 10.1038/s41380-020-0806-5

Affiliations: 28

Authors: 49

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Research Highlight

All about that BACE2

© GSO Images/Getty

© GSO Images/Getty

Brain organoids grown from the reprogrammed hair cells of people with Down syndrome have revealed a gene that can act as a natural suppressor of Alzheimer’s disease.

Around 70% of people with Down syndrome develop dementia during their lifetimes. This is because, with three copies of chromosome 21, they inherit an extra copy of a gene involved in making amyloid-β, the sticky protein that can clump in the brain, leading to neuronal loss.

A similar percentage of the lab-grown ‘mini brains’ created by scientists at Nanyang Technological University, Singapore, and elsewhere also showed the hallmark features of Alzheimer’s disease. The pathology could be induced, however, by genetically eliminating the third copy of BACE2, a gene found on chromosome 21.

The researchers detailed how BACE2 acts as a dose-sensitive suppressor of Alzheimer’s — a finding that could now be exploited therapeutically to forestall neurodegeneration in people both with and without Down syndrome.

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  1. Molecular Psychiatry (2020) doi: 10.1038/s41380-020-0806-5
Institutions Share
Lee Kong Chian School of Medicine, Singapore 0.19
Department of Psychiatry and Neurochemistry, GU, Sweden 0.11
London Down Syndrome Study (LonDownS), United Kingdom (UK) 0.09
School of Medicine, University of Zagreb, Croatia 0.08
Blizard Institute, QMUL, United Kingdom (UK) 0.07
UCL Division of Psychiatry, United Kingdom (UK) 0.04
NYU Robert I. Grossman School of Medicine, United States of America (USA) 0.04
UCL Department of Neuromuscular Diseases, United Kingdom (UK) 0.04
UK DRI at UCL (UK DRI UCL), United Kingdom (UK) 0.04
School of Biological Sciences (SBS), NTU, Singapore 0.04
Laboratory of Genomic and Personalized Medicine in Cancer and Neurological Disorders, France 0.04
Genome Institute of Singapore (GIS), A*STAR, Singapore 0.03
Department of Forensic and Neurodevelopmental Sciences, KCL, United Kingdom (UK) 0.02
Wolfson Centre for Age-Related Diseases (Wolfson CARD), KCL, United Kingdom (UK) 0.02
UCL Division of Biosciences, United Kingdom (UK) 0.02
School of Life Sciences, University of Westminster, United Kingdom (UK) 0.02
Institute of Clinical Medicine, UEF, Finland 0.02
Birkbeck, University of London (BBK), United Kingdom (UK) 0.02
Institute of Medical Biology (IMB), A*STAR, Singapore 0.01
UCL Reta Lila Weston Institute (RLWI), United Kingdom (UK) 0.01
Department of Medicine (DOM), ICL, United Kingdom (UK) 0.01
The Francis Crick Institute, United Kingdom (UK) 0.01
Faculty of Veterinary Medicine, University of Zagreb, Croatia 0.01