Neurodegeneration in Aging Down Syndrome (NiAD)
Research type
Research Study
Full title
Neurodegeneration in Aging Down Syndrome (NiAD): A Longitudinal Study of Cognition and Biomarkers of Alzheimer's Disease.
IRAS ID
196116
Contact name
John T. O'Brien
Contact email
Sponsor organisation
Cambridgeshire and Peterborough NHS Foundation Trust & University of Cambridge (joint sponsors)
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Research Summary
Down’s syndrome (DS) occurs in 1 in 800 to 1000 live births and is caused by having three copies of chromosome 21 instead of the usual two. This has serious consequences for the health of people with DS, including an increased risk for Alzheimer’s disease (AD). This is most likely due to people with DS having an extra copy of the APP gene, which is located on chromosome 21, causing an over-production of “beta-amyloid” (A-beta) protein and resulting in AD. Almost all people with DS develop brain tissue changes in specific parts of the brain – deposits of tau and A-beta proteins – that characterise the pathology of AD. It is some 10 to 15 years later when the clinical manifestations of AD become apparent in a majority of people with DS, by which time is it is more difficult for disease-modifying treatments to be effective. Therefore, there is a need to define and understand the “pre-clinical” AD state to help identify possible early treatment targets or avenues. By studying the pre-clinical course of AD in DS we aim to indentify the earliest indicators (biomarkers) of those who will develop clinical dementia. We aim to follow up, over a five year period, a cohort of people with DS aged 25 years and older, to help to understand features that predict those who will develop AD. We aim to measure levels of brain tau and A-beta with positron emission tomography (PET) and magnetic resonance imaging (MRI). We will also measure brain electrical activity with electroencephalograpyh (EEG) and obtain blood and spinal fluid samples in order to unravel their relation to dementia, brain structure and cognitive function. We have used similar techniques in our recent projects, but we now wish to extend the study and monitor participants prospectively over 5 years. We will be one of the sites in a USA-led multi-site consortium. The research will be conducted in Cambridge.
Summary of Results
Given the extensive amount of data that we collected from our participants, and the length of data collection and number of participants involved, the results of the study have been extensive. A key aim of NiAD was to study biomarkers (things in the body that change as a disease develops) of Alzheimer's disease (AD) in Down's syndrome (DS). Two key chemicals have been linked to AD development in DS, called amyloid and tau. NiAD findings have added to the literature on the importance of amyloid and tau for AD in DS, studying the impact of these chemicals on brain structure using brain imaging (see degeneration, or shrinking, in those with AD), and looking at these chemicals in the blood and spinal fluid (found higher levels of these chemicals in those with AD). Analyses have shown that cognitive decline follows on from accumulation of first amyloid and then tau.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
16/YH/0297
Date of REC Opinion
25 Aug 2016
REC opinion
Further Information Favourable Opinion