HAI Book 2025 - Flipbook - Page 705
Salvadó, Gemma
Plasma tau biomarkers and staging of Alzheimer9s disease
Gemma Salvadó1, Laia Montoliu-Gaya2, Joseph Therriault3, Johanna Nilsson2, Shorena
Janelidze1, Sophia Weiner2, Nicholas J Ashton2,4, Andrea L Benedet2, Juan LanteroRodríguez2, Niklas Mattsson-Carlgren1, Sebastian Palmqvist1,10, Gunnar Brinkmalm2, Erik
Stomrud1,10, Henrik Zetterberg2,5,6,7,8, Johan Gobom2, Pedro Rosa-Neto3, Kaj Blennow6, Oskar
Hansson1,10
1
Lund University, Lund, SE
University of Gothenburg, Mölndal, SE
3
McGill University, Montreal, QC, CA
4
Banner Institute, Phoenix, AZ, US
5
Sahlgrenska University Hospital, Mölndal, SE
6
University College London, London, GB
7
UK Dementia Research Institute, London, GB
8
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, CN
9
UW Department of Medicine, Madison, WI, US
10
Memory Clinic, Skåne University Hospital, Malmö, SE
2
Introduction: Staging Alzheimer9s disease (AD) can enhance diagnosis, prognosis, and the selection of patients
most likely to benefit from targeted biological therapies. Plasma biomarkers offer a scalable alternative to PET
tracers for classifying individuals across the AD continuum.
Methods: We utilized targeted mass spectrometry to measure six phosphorylated (p-tau) and six nonphosphorylated tau (np-tau) peptides in the BioFINDER-2 cohort (n=549), which included individuals in the whole
AD continuum. Differences in each p-tau biomarker were evaluated by diagnostic group. Three tau biomarkers4
plasma p-tau217r (ratio of p-tau217/np-tau217), p-tau205r, and 0N-tau4were chosen to develop a disease-staging
system using k-means clustering. The model was trained using 10-fold cross-validation, so individuals classified
by the model were different from those used in the model creation. Associations between plasma stages and
other AD biomarkers were examined cross-sectionally and longitudinally. The staging model was validated in the
independent TRIAD cohort (n=140).
Results: Plasma p-tau217r, p-tau205r, and 0N-tau demonstrated the largest increases across distinct diagnostic
groups (cognitively unimpaired amyloid-´ [A´]-positive, mild cognitive impairment A´-positive, and AD dementia,
respectively; Figure 1). Higher plasma stages were linked to abnormalities in key AD biomarkers, including A´-PET,
tau-PET, AD-signature cortical thickness, and cognitive performance, in both cohorts (Figure 2). Additionally, in
BioFINDER-2, higher plasma stages correlated with faster disease progression, as indicated by longitudinal tauPET accumulation, cortical atrophy and cognitive decline (Figure 3).
Conclusions: We developed and validated a plasma-staging model in two independent cohorts, demonstrating its
strong associations with AD disease status and progression. This scalable model could facilitate monitoring in
clinical settings and aid in selecting participants for trials targeting specific biological pathways.
HAI2025 - 705
