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Alzheimer's disease in people with Down's syndrome: the prospects for and the challenges of developing preventative treatments.

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Castro, Paula 
Zaman, Shahid 


People with Down's syndrome (DS) are at high risk for developing Alzheimer's disease (AD) at a relatively young age. This increased risk is not observed in people with intellectual disabilities for reasons other than DS and for this reason it is unlikely to be due to non-specific effects of having a neurodevelopmental disorder but, instead, a direct consequence of the genetics of DS (trisomy 21). Given the location of the amyloid precursor protein (APP) gene on chromosome 21, the amyloid cascade hypothesis is the dominant theory accounting for this risk, with other genetic and environmental factors modifying the age of onset and the course of the disease. Several potential therapies targeting the amyloid pathway and aiming to modify the course of AD are currently being investigated, which may also be useful for treating AD in DS. However, given that the neuropathology associated with AD starts many years before dementia manifests, any preventative treatment must start well before the onset of symptoms. To enable trials of such interventions, plasma, CSF, brain, and retinal biomarkers are being studied as proxy early diagnostic and outcome measures for AD. In this systematic review, we consider the prospects for the development of potential preventative treatments of AD in the DS population and their evaluation.



Alzheimer’s disease, Biomarkers, Down syndrome, Treatment, Adult, Alzheimer Disease, Down Syndrome, Humans

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J Neurol

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Springer Science and Business Media LLC
Medical Research Council (G1002252)
We would like to acknowledge the following organisations that have provided financial support: the Brazilian National Council of Technological and Scientific Development (CNPq), the Medical Research Council (MRC), Alzheimer’s Research UK (AR-UK), the Health Foundation, the UK Down’s Syndrome Association, the NIHR CLARHC for the East of England, and Research Capacity Funding from Cambridgeshire and Peterborough Foundation NHS Trust. Shahid Zaman and Anthony Holland hold clinical consultant contracts with Cambridgeshire and Peterborough NHS Foundation Trust. Paula Castro is a medical student from the Faculty of Medicine of Jundiai, Brazil, and was on attachment to Anglia Ruskin University, Cambridge, and undertook an internship with the Cambridge Intellectual and Developmental Disabilities Research Group in the Department of Psychiatry at the University of Cambridge.