Consequences of trisomy 21 for brain development in Down syndrome

Matthew L Russo; André M M Sousa; Anita Bhattacharyya

doi:10.1038/s41583-024-00866-2

Consequences of trisomy 21 for brain development in Down syndrome

Nat Rev Neurosci. 2024 Oct 8. doi: 10.1038/s41583-024-00866-2. Online ahead of print.

Authors

Matthew L Russo¹, André M M Sousa^{1

2}, Anita Bhattacharyya^{3

4}

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
² Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
³ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA. bhattacharyy@waisman.wisc.edu.
⁴ Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. bhattacharyy@waisman.wisc.edu.

PMID: 39379691
DOI: 10.1038/s41583-024-00866-2

Abstract

The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field.

Publication types

Review