Associated organisationsBirkbeck, University of London · Misc England · Queen Mary University of London · The Francis Crick Institute · University College LondonEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£2.7M
PeriodDec 2012 — Nov 2018
In plain English
AI plain-English summary
Every person with Down syndrome develops Alzheimer’s pathology in the brain, yet only some go on to develop dementia—and no one knows why. This consortium is tackling that puzzle head-on. Most studies treat Down syndrome as a single condition, but this project focuses on the wide variation between individuals. The researchers will track cognitive development in infants, adults, and mouse models using comparable assessments, then link those profiles to cellular and genetic differences—including defects in neuron formation, mitochondrial function, and amyloid-beta accumulation—using neurons grown from participants’ own stem cells. They will also build a biobank and genotype-phenotype database to support future drug trials and imaging studies. If the team can identify which biological markers predict dementia decades before symptoms appear, early diagnosis and targeted intervention become realistic. That could shift care from managing decline to preventing it. The work is also timely: therapies for cognitive deficits in Down syndrome are now within reach, but they need precise subgroups to test against. This project provides the map.
View original technical description
Most studies treat Down syndrome (DS) as a single entity. Our novel aim is to focus on individual differences and subgroups at the cellular, genetic and cognitive levels to explain why the DS phenotype varies so much. For example, despite all DS individuals presenting with Alzheimer's Disease pathology, only a subgroup develops dementia. Is this due to cellular, molecular, genetic and/or cognitive differences? Can we identify these differences not only in adulthood, but also in infancy? If so, early diagnosis and intervention can be targeted. To study DS cognition longitudinally, we will develop comparable assessments for DS infants, adults and mouse models, to characterise deficits associated with hippocampal, cerebellar and frontal regions. Uniquely, we will correlate cognitive/genetic profiles with defects in neurogenesis, neurite/synapse plasticity, mitochondrial dysfunction, A-beta accumulation within participants neurons, differentiated from iPSC. We will create a Biobank and genotype/phenotype database as platforms for add-on pharmacologic/metabolomic/imaging projects, and clinical trials. This project aligns methods with other DS studies globally, but is unique in encompassing different age cohorts, integrating human cognitive development, ageing, neurobiology, genetics, cellular and mouse modelling. It is strategic for improved health, and timely, as therapies for DS cognitive deficits and decline are now realistic.
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