P2.42. A NOVEL CROSS-SPECIES P-TAU217 IMMUNOASSAY FOR INVESTIGATING ANIMAL MODELS OF ALZHEIMER'S DISEASE
Alberto González-Mayoral1, Fernando Gonzalez-Ortiz2, Marie-Claude Potier1, Kaj Blennow1,2,3, Nicolas Villain1,4
1 Sorbonne Université, INSERM U1127, CNRS 7225, Paris Brain Institute - PBI, Paris, France
2 University of Gothenburg, Department of Psychiatry And Neurochemistry, Institute of Neuroscience And Physiology, The Sahlgrenska Academy At The University Of Gothenburg, Mölndal, Sweden
3 Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden
4 Département de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP Sorbonne Université, Institute of Memory and Alzheimer’s Disease, Paris, France
INTRODUCTION: The measurement of phosphorylated tau (pTau) in biofluids, particularly at position 217 (pTau217), has proven to be a valuable diagnostic and prognostic marker in Alzheimer’s disease (AD). However, due to tau variability across species existing immunoassays lack compatibility with mouse models, posing a challenge for studying these markers in preclinical research.
AIM(S): Development and optimization of a novel cross-species p-tau217 immunoassay to investigate animal models of AD.
METHOD(S): A novel pTau217 immunoassay was developed and validated on the Simoa platform with plasma samples from three distinct mouse models containing either endogenous or transgenic human tau (APP23, P301S and WT) and human plasma samples for cross-species validation. Optimization for sensitivity, specificity, and reproducibility included different antibodies concentration tests, limit of quantification, and buffer adjustments to diminish plasma matrix interference.
RESULTS: The sequence alignment guided the selection of antibodies targeting conserved epitopes, ensuring cross-species applicability. The novel pTau217 immunoassay, based on Simoa technology, demonstrated good performance in detecting pTau in brain extracts and plasma across all three mouse models containing endogenous mouse tau and transgenic human tau. It also proved to detect human plasma pTau217. The assay exhibited high sensitivity, achieving reliable detection of pTau even in plasma samples with low abundant protein concentrations and matrix interference effect, and showed robust specificity to pTau217.
CONCLUSIONS: We present the validation of the first Simoa-based pTau217 immunoassay designed to measure p-tau across species (mouse and human), whether in plasma samples with genuine mouse tau sequence or transgenic human tau sequence. Further development will focus on linearity tests and correlation with neuropathologic changes. Our findings have broad implications for biomarkers research and help bridge the gap between human and animal studies in AD research.
FINANCIAL SUPPORT: Fondation Recherche Alzheimer
Paris Brain Institute (PBI)