Fluid biomarkers for Alzheimer's disease in Down syndrome: Current status and novel trends

Abstract Down syndrome (DS) is one of the most commonly occurring genetic chromosomal disorders, with a worldwide incidence of about 1 in 1000 births. Individuals with DS exhibit Alzheimer's disease (AD) pathology with almost complete penetration, and with symptoms occurring in their 40s or 50s. However, because AD pathology occurs early in people with DS, there is a window for implementing preventative treatment, strongly suggesting that prognostic biomarkers of AD need to be developed and standardized. Although there are several fluid biomarkers that are significantly altered in DS compared to non-DS populations, candidate markers capable of distinguishing between AD-symptomatic and asymptomatic individuals with DS are less established. This chapter focuses on providing information regarding the latest findings on blood and CSF biomarkers in DS, including classical markers of AD pathology and neurodegeneration (Aβ, Tau, and NfL), as well as highlighting novel biomarker candidates, including inflammation, oxidative stress, miRNAs, and extracellular vesicles.