Noëlle Warmenhoven - Institutionen för kliniska vetenskaper, Malmö

Title: Investigating the potential of blood-based biomarkers for neurodegenerative diseases

Supervisors: Assoc. Prof. Sebastian Palmqvist 

Reviewers: Assoc. Prof. Elena Rodriguez-Vieitez and Asst. Prof. Andrea Benedet

Abstract

Background

Blood-based biomarkers (BBMs) for neurodegenerative diseases have experienced a spike in interest over the past few years, especially for Alzheimer's disease (AD), as cost-effective, scalable and non-invasive biomarkers. Although several well-performing BBMs for AD have been identified, challenges remain before BBMs can be implemented in real-world clinical settings. 

Research questions

The thesis will focus on analysing clinical data to address critical questions to facilitate BBM integration into clinical routine, such as: i) whether BBMs outperform gold-standard cerebrospinal fluid (CSF) biomarkers ii) what measurement techniques should be used, and iii) whether BBMs can be used as prognostic tools. Data from the Swedish BioFINDER cohorts and other AD research cohorts will be used. 

Preliminary results

Project I (published): This study compared different plasma p-tau217 biomarker tests to each other, for detection of AD pathology and cognitive decline. Plasma %p-tau217 with mass-spectrometry was consistently the best performing plasma p-tau217 biomarker test and often outperformed CSF biomarkers.

Project II (published): In this study, the performance of plasma p-tau217 measured on a fully automated platform for detecting AD pathology was assessed in five different cohorts, including one from primary care. The fully automated p-tau217 test demonstrated high accuracy for identifying AD pathology across different clinical populations.

Project III (data analysis): Plasma p-tau217 measured on a fully automated platform to detect AD pathology is currently undergoing FDA-approval for AD diagnosis. This project will compare how these plasma biomarkers perform relative to current gold-standard CSF biomarkers.

Project IV (data collection): With the recent approval of anti-amyloid therapies, the question remains whether cognitively unimpaired (CU) individuals should receive these as part of a secondary prevention strategy. The absolute risk of developing dementia will be assessed in CU participants, in plasma p-tau217+ versus p-tau217- participants, to simultaneously assess its screening potential.

Project V (planned): Evidence suggests impaired immune functioning across the AD continuum, but identifying AD-specific inflammatory markers in blood may be challenging due to peripheral influences. This project will assess whether inflammatory plasma biomarkers hold accurate prognostic value.

Significance

Establishing scalable and cost-effective biomarkers for AD may help ensure an accurate AD diagnosis and prognosis. 

Published studies

Warmenhoven, N. et al. (2024). Comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests. Brain. 148(2), 416-431. https://doi.org/10.1093/brain/awae346. 

Palmqvist, S., Warmenhoven, N. ss& Anastasi, F. et al. (2025). Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform. Nat Med (2025). https://doi.org/10.1038/s41591-025-03622-w