The locus coeruleus:
at the crossroad of dementia syndromes

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

Ivan Alić, Pollyanna A Goh, Aoife Murray, Erik Portelius, Eleni Gkanatsiou, Gillian Gough, Kin Y Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L O'Brien, Jürgen Groet, Xiaowei Shao, Steven Havlicek, N Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin, Sarah Hamburg, Margaret Phillips, Konstantin Pervushin, Mark Turmaine, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E Martin, Jia Nee Foo, David L Becker, Agueda Rostagno, Jorge Ghiso, Željka Krsnik , Goran Šimić, Ivica Kostović , Dinko Mitrečić , LonDownS Consortium; Paul T Francis, Kaj Blennow , Andre Strydom, John Hardy, Henrik Zetterberg, Dean Nižetić.

Mol Psychiatry. 2020 Jul 10. doi: 10.1038/s41380-020-0806-5.

The article reported AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The results prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. Authors also showed that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens.

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