Blood‐based biomarkers for Alzheimer’s Disease in Down Syndrome

Abstract

AbstractBackgroundPeople with DS are at high risk to develop Alzheimer’s disease dementia (AD) (Lott & Head, 2001). Predicting and monitoring decline and onset of dementia is a diagnostic challenge and of essence in daily care and support for people with DS. Behavioral and Psychological Symptoms of Dementia (BPSD) are an easily accessible tool for the prediction of dementia onset in the DS population. The BPSD‐DS II scale was developed and validated by our team to identify behavioral changes linked to AD between the last six months and pre‐existing behavior in an individual with DS (Dekker et al., 2021). This project is based on a cohort of DS individuals without AD (n = 94), with AD (n = 43), or with questionable AD (qAD) (n = 54) aged >35 years. At inclusion, the BPSD‐DS II was applied to assess AD‐linked behavioral changes, and biofluid sampling was performed as well. Changes in cerebrospinal fluid (CSF) levels of monoaminergic neurotransmitters and metabolites have been associated with BPSD in AD (Dekker et al., 2015). However, CSF sampling procedures remain difficult in DS, illustrating the need for blood biomarkers. BPSD‐DS II results will be correlated with the serum levels of monoaminergic and classical AD biomarkers. Three years post‐inclusion, a follow‐up study was conducted to assess the evolution of possible AD dementia within this group and to determine the predictive values of the BPSD‐DS II scale and the different analytes.MethodWe will use reversed‐phase ultra‐high performance liquid chromatography with electrochemical detection to determine the levels of (nor)epinephrine, dopamine, serotonin and their metabolic products in serum. We will use the Simoaâ platform on the serum of clients with DS without or with (q)AD to detect the levels of Ab40, Ab42, total tau, phosphorylated tau, Glial Fibrillary Acidic Protein and Neurofilament Light chain.ResultWe expect a correlation between the results of the BPSD‐DS II and the levels of the monoamines and classical biomarkers in patients with DS without or with (q)AD.ConclusionThe diagnosis predicted by the results of the BPSD‐DS II correlates with the levels of monoamines and classical biomarkers in individuals with DS without or with (q)AD.