Blood‐based biomarkers for clinical trials of Alzheimer’s disease in Down syndrome

Abstract

AbstractBackgroundA blood biomarker for a clinical diagnosis of Alzheimer’s disease (AD) is of particular importance in Down syndrome, where a change in cognitive function is often difficult to delineate. Recent advances in ultra‐sensitive detection methods have allowed for the quantification of GFAP, p‐tau and NfL, which demonstrate high specificity for diagnosis of AD pathology and neurodegeneration, which has been utilised in recent anti‐amyloid trials.MethodsNovel data presented in this talk will compare a multi‐centre study (n>800) on plasma NfL, GFAP, and phosphorylated tau (p‐tau181, p‐tau217, p‐tau231) from sporadic AD, familial AD, adults with Down syndrome and euploid controls in a cross‐sectional and longitudinal manner.ResultsWe compared plasma biomarker performance to monitor clinical progression or identify changes in 18F‐fluorodeoxyglucose, amyloid PET and cortical atrophy by MRI. Further, explorative proteomics in cerebrospinal fluid (CSF) aims to identify novel candidates of clinical decline in Down syndrome individuals. Lastly, novel pilot data demonstrate that measures of GFAP, NfL and p‐tau are possible via capillary blood, extracted from a finger prick test, which have important implications as an off‐site blood collection in the Down Syndrome community without the need for strict blood processing protocols.ConclusionPlasma biomarkers of sporadic AD, specifically GFAP, NfL and p‐tau217, have equally high performance to AD pathology in Down Syndrome individuals with possible applications in clinical practice and clinical trials. Moreover, GFAP and NfL may act as important biomarkers in an off‐site finger prick collection which will increase inclusion and easier monitoring in the Down Syndrome community.