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Review
. 2025 Apr;12(4):100056.
doi: 10.1016/j.tjpad.2024.100056. Epub 2025 Jan 14.

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use

M Schöll  1 , A Vrillon  2 , T Ikeuchi  3 , F C Quevenco  4 , L Iaccarino  4 , S Z Vasileva-Metodiev  4 , S C Burnham  4 , J Hendrix  4 , S Epelbaum  4 , H Zetterberg  5 , S Palmqvist  6
Affiliations
Review

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use

M Schöll et al. J Prev Alzheimers Dis. 2025 Apr.

Abstract

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic. We focus on plasma phosphorylated(p)-tau, specifically plasma p-tau217, as a robust candidate across both primary and secondary care settings. Despite the high performance and robustness demonstrated in research, plasma p-tau217, like all plasma biomarkers, can be affected by analytical and pre-analytical variability as well as patient comorbidities, sex, ethnicity, and race. This review also discusses the advantages of the two-point cut-off approach to mitigating these factors, and the challenges raised by the resulting intermediate range measurements, where clinical guidance is still unclear. Further validation of plasma p-tau217 in heterogeneous, real-world cohorts will help to increase confidence in testing and support establishing a standardized approach. Plasma biomarkers are poised to become a more affordable and less invasive alternative to PET and CSF testing. However, understanding the factors that impact plasma biomarker measurement and interpretation is critical prior to their implementation in routine clinical use.

Keywords: Alzheimer's disease; Biomarkers; Clinical routine; Neurodegeneration; Plasma.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frances-Catherine Quevenco reports administrative support, article publishing charges, and writing assistance were provided by Eli Lilly and Company. Michael Schöll reports a relationship with BioArctic AB that includes: funding grants, speaking and lecture fees, and travel reimbursement. Michael Schöll reports a relationship with Roche Diagnostics Corporation that includes: funding grants and speaking and lecture fees. Michael Schöll reports a relationship with Novo Nordisk Inc that includes: speaking and lecture fees. Michael Schöll reports a relationship with Triolabs that includes: speaking and lecture fees. Michael Schöll reports a relationship with Centile Bioscience that includes: equity or stocks. Sebastian Palmqvist reports a relationship with Avid Radiopharmaceuticals Inc that includes: funding grants. Sebastian Palmqvist reports a relationship with Alzheimer's Drug Discovery Foundation that includes: funding grants. Sebastian Palmqvist reports a relationship with Eisai Inc that includes: consulting or advisory and travel reimbursement. Sebastian Palmqvist reports a relationship with Roche Diagnostics Corporation that includes: consulting or advisory and speaking and lecture fees. Sebastian Palmqvist reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Sebastian Palmqvist reports a relationship with BioArctic AB that includes: consulting or advisory and travel reimbursement. Sebastian Palmqvist reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and travel reimbursement. Agathe Vrillon reports a relationship with A2MCL that includes: funding grants and travel reimbursement. Agathe Vrillon reports a relationship with Bioprojet that includes: funding grants. Agathe Vrillon reports a relationship with Foundation Overcoming Alzheimer that includes: funding grants. Agathe Vrillon reports a relationship with France Alzheimer that includes: travel reimbursement. Takeshi Ikeuchi reports a relationship with Japan Agency for Medical Research and Development that includes: funding grants. Takeshi Ikeuchi reports a relationship with Eisai Inc that includes: speaking and lecture fees. Takeshi Ikeuchi reports a relationship with FUJIREBIO Inc that includes: speaking and lecture fees. Takeshi Ikeuchi reports a relationship with Eli Lilly and Company that includes: speaking and lecture fees. Frances-Catherine Quevenco reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. Leonardo Iaccarino reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. Simona Z. Vasileva-Metodiev reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. Samantha C. Burnham reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. James Hendrix reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. Stephane Epelbaum reports a relationship with Eli Lilly and Company that includes: employment and equity or stocks. Henrik Zetterberg reports a relationship with AD Strategic Fund (Alzheimer's Association) that includes: funding grants. Henrik Zetterberg reports a relationship with Alzheimer's Drug Discovery Foundation that includes: funding grants. Henrik Zetterberg reports a relationship with Bluefield Project that includes: funding grants. Henrik Zetterberg reports a relationship with Cure Alzheimer's Fund that includes: funding grants. Henrik Zetterberg reports a relationship with Erling Persson Family Foundation that includes: funding grants. Henrik Zetterberg reports a relationship with EU Joint Programme Neurodegenerative Disease Research that includes: funding grants. Henrik Zetterberg reports a relationship with Hjärnfonden that includes: funding grants. Henrik Zetterberg reports a relationship with Horizon Europe that includes: funding grants. Henrik Zetterberg reports a relationship with National Institute for Health and Care Research UCLH Biomedical Research centre that includes: funding grants. Henrik Zetterberg reports a relationship with Olav Thon Foundation that includes: funding grants. Henrik Zetterberg reports a relationship with Stiftelsen för Gamla Tjänarinnor that includes: funding grants. Henrik Zetterberg reports a relationship with Swedish Research Council that includes: funding grants. Henrik Zetterberg reports a relationship with Swedish State Support for Clinical Research that includes: funding grants. Henrik Zetterberg reports a relationship with UK Dementia Research Institute that includes: funding grants. Henrik Zetterberg reports a relationship with AbbVie Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Acumen Pharmaceuticals, Inc. that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Alector Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Alzinova AB that includes: consulting or advisory. Henrik Zetterberg reports a relationship with ALZPath that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Amylyx Pharmaceuticals Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Annexon Biosciences that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Apellis Pharmaceuticals, Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Artery Therapeutics Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with AZTherapies that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Cognito Therapeutics that includes: consulting or advisory. Henrik Zetterberg reports a relationship with CogRx that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Denali Therapeutics Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Eisai Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with LABCORP that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Merry Life Biomedical that includes: consulting or advisory. Henrik Zetterberg reports a relationship with NervGen Pharma Corp that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and speaking and lecture fees. Henrik Zetterberg reports a relationship with Optoceutics that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Passage Bio Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Pinteon Therapeutics Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Prothena Biosciences Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Red Abbey Labs that includes: consulting or advisory. Henrik Zetterberg reports a relationship with reMYND that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Roche Diagnostics Corporation that includes: consulting or advisory and speaking and lecture fees. Henrik Zetterberg reports a relationship with Samumed that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Siemens Healthineers AG that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Triplet Therapeutics Inc that includes: consulting or advisory. Henrik Zetterberg reports a relationship with Wave that includes: consulting or advisory. Henrik Zetterberg reports a relationship with AlzeCure Pharma that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with Biogen Inc that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with Cellectricon AB that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with Eli Lilly and Company that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with FUJIREBIO Inc that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with WebMD LLC that includes: speaking and lecture fees. Henrik Zetterberg reports a relationship with Brain Biomarker Solutions in Gothenburg AB that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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