Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics

Author:

Arslan Burak12,Zetterberg Henrik12345,Ashton Nicholas J.16789

Affiliation:

1. Department of Psychiatry and Neurochemistry , Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , Mölndal , Sweden

2. Clinical Neurochemistry Laboratory , Sahlgrenska University Hospital , Mölndal , Sweden

3. Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health , University of Wisconsin-Madison , Madison , WI , USA

4. Department of Neurodegenerative Disease , UCL Institute of Neurology , London , UK

5. UK Dementia Research Institute at UCL , London , UK

6. Department of Old Age Psychiatry, Psychology & Neuroscience , King’s College London, Institute of Psychiatry , London , UK

7. King’s College London , Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute , London , UK

8. NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley, NHS Foundation , London , UK

9. Centre for Age-Related Medicine , Stavanger University Hospital , Stavanger , Norway

Abstract

Abstract Alzheimer’s disease (AD), a primary cause of dementia globally, is traditionally diagnosed via cerebrospinal fluid (CSF) measures and positron emission tomography (PET). The invasiveness, cost, and limited accessibility of these methods have led to exploring blood-based biomarkers as a promising alternative for AD diagnosis and monitoring. Recent advancements in sensitive immunoassays have identified potential blood-based biomarkers, such as Aβ42/Aβ40 ratios and phosphorylated tau (p-tau) species. This paper briefly evaluates the clinical utility and reliability of these biomarkers across various AD stages, highlighting challenges like refining plasma Aβ42/Aβ40 assays and enhancing the precision of p-tau, particularly p-tau181, p-tau217, and p-tau231. The discussion also covers other plasma biomarkers like neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and synaptic biomarkers, assessing their significance in AD diagnostics. The need for ongoing research and development of robust assays to match the performance of CSF and PET biomarkers is underscored. In summary, blood-based biomarkers are increasingly crucial in AD diagnosis, follow-up, prognostication, treatment response evaluation, and population screening, particularly in primary care settings. These developments are set to revolutionize AD diagnostics, offering earlier and more accessible detection and management options.

Funder

HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council

European Union’s Horizon Europe research and innovation programme

Swedish State Support for Clinical Research

Alzheimer Drug Discovery Foundation (ADDF), USA

AD Strategic Fund and the Alzheimer’s Association

Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden

European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie

European Union Joint Programme – Neurodegenerative Disease Research

National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL

Publisher

Walter de Gruyter GmbH

Subject

Biochemistry (medical),Clinical Biochemistry,General Medicine

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