Abstract

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work is needed. Findings from stability work of blood-based biomarkers conducted among non-DS also support the potential longitudinal utility of biomarkers such as neurofilament light chain and p-tau181 in DS. Gaps in our knowledge are highlighted, and a potential role for sex differences in biomarker outcomes is noted, along with recommendations for determining the appropriate context of use when translating biomarkers into clinical applications.

Document Type

Article

Publication Date

1-2025

Notes/Citation Information

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Digital Object Identifier (DOI)

https://doi.org/10.1002/alz.14364

Funding Information

Medical Research Council, Grant/Award Numbers: MR/S011277/1, MR/ S005145/1, MR/R024901/1; European Commission, Grant/Award Numbers: 1R61AG066543-01, GO-DS21-848077; Alzheimer’s Society, Grant/Award Number: AS-CP-18-0020; Fondo de Investigaciones Sanitario, Carlos III Health Institute, Grant/Award Number: PI20/01473; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas; National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL, Grant/Award Number: UKDRI-1003; European Union Joint Programme—Neurodegenerative Disease Research, Grant/Award Number: JPND2021-00694; AD Strategic Fund and Alzheimer’s Association, Grant/Award Numbers: ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C; Alzheimer’s Drug Discovery Foundation, Grant/Award Number: 201809-2016862; HORIZON EUROPE Framework Programme, Grant/Award Number: 101053962; National Institute of Biomedical Imaging and Bioengineering, Grant/Award Number: P41EB015922; Horizon 2020- Research and Innovation Framework Programme from the European Union, Grant/Award Numbers: H2020-SC1-BHC-2018-2020, Marie Sklodowska-Curiegrant agreement No 860197 (MIRIADE); Departament de Salut, Generalitat de Catalunya, Grant/Award Number: SLT006/17/00119; Alzheimer Society, Grant/Award Number: AS-CP-18-0020; Foundation for the National Institutes of Health, Grant/Award Numbers: U19AG078109, U19AG068054, RF1AG079519, 1R61AG066543-01, 1R01AG056850-01A1, R21AG056974, R01AG061566, R01AG054073, R01AG058533; Alzheimer’s Association, Grant/Award Number: 23AARFD-1022715; Swedish State Support for Clinical Research, Grant/Award Number: ALFGBG-71320; Blue- field Project; Olav Thon Foundation; Erling-Persson Family Foundation; Stiftelsen for Gamla Tjanarinnor, Grant/Award Number: F02022-0270; Swedish Research Council, Grant/Award Numbers: 2022-01018, 2019-02397; Jérôme Lejeune Foundation

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