Advances in Alzheimer’s biomarker science have transformed early detection and stratification, laying the groundwork for more personalized approaches to care. Yet as the field shifts toward tracking disease dynamics with greater precision, the next frontier lies in capturing the full trajectory of tau pathology, spanning its earliest biochemical shifts to the later-stage neurofibrillary changes that drive clinical decline. To address this need, Quanterix has expanded its tau biomarker portfolio with p-Tau 205 and p-Tau 212, two assays designed to provide complementary insights into the temporal, spatial, and molecular diversity of tau pathology. 

With the addition of p-Tau 205 and p-Tau 212 to its Simoa^® assay portfolio, Quanterix is advancing a more nuanced and complete framework for tau-based Alzheimer’s profiling. These new markers offer distinct biological insights and detection capabilities that complement existing assays like p-Tau 181, p-Tau 217, total tau, and brain-derived tau (BD-Tau). Quanterix is first to market with both p-Tau 205 and p-Tau 212 assays, providing researchers with a head start in adopting next-generation tau markers. Together, they support a comprehensive, stage-aware strategy for research, drug development, and precision medicine. 

Expanding the Tau Landscape 

Tau pathology is not monolithic. It is a progressive, multi-step process involving site-specific phosphorylation events, structural rearrangements, and spatial spreading through the brain. Existing biomarkers such as p-Tau 181 and p-Tau 217 have illuminated critical early pathological changes, particularly those correlated with amyloid PET positivity and incipient neurodegeneration. 

However, phosphorylation sites such as threonine 205 (p-Tau 205) and threonine 212 (p-Tau 212) provide access to additional biological terrain. These sites represent key transitions in tau’s aggregation cascade, capturing shifts in conformation, regional accumulation, and clinical severity. Their inclusion helps trace a more continuous and mechanistic narrative of disease progression. 

Mechanistic Relevance in Tau Pathogenesis 

Phosphorylation at threonine 205 and 212 represents more than a molecular tag, it reflects crucial shifts in tau’s structure, function, and behavior. p-Tau 205 and p-Tau 212 are positioned within proline-directed kinase target regions implicated in the transformation of tau from a stabilizing cytoskeletal protein to an aggregation-prone neurotoxic species. Threonine 205 phosphorylation has been linked to loss of microtubule binding and alignment with PHF-tau pathology, while p-Tau 212 is observed in disease-enriched conformational states, including paired helical filaments and ghost tangles. These sites are downstream events relative to amyloid accumulation, making them ideal for tracking the progression to tau-mediated neurodegeneration. Including them in biomarker panels introduces the ability to interrogate mid-to-late stage mechanisms more precisely and explore therapeutic hypotheses centered on disease propagation and toxicity. 

Key Biological Insights from p-Tau 205 

• CSF p-Tau 205 shows strong correlation with tau-PET signal and Braak stage, positioning it as a sensitive proxy for neurofibrillary tangle burden. 
• p-Tau 205 tends to rise later in the disease process, corresponding to advanced tau aggregation rather than early amyloid-induced changes. 
• It correlates closely with measures of cognitive decline and regional brain atrophy, making it useful for assessing disease severity and progression. 
• The Simoa^®-based immunoassay enables quantification with high precision in serum, plasma, and CSF, supporting diverse study designs and patient cohorts. 

Key Biological Insights from p-Tau 212 

• Rises early in AD pathogenesis, prior to overt cognitive symptoms, and continues to increase with disease progression. 
• Reflects conformational states of tau that differ from those captured by p-Tau 181 and p-Tau 217. 
• Correlates with central pathology and clinical outcomes, including PET signal and cognitive decline. 
• Can be robustly measured in serum, plasma, and CSF, making it well suited for scalable, non-invasive monitoring in clinical and research contexts. 

Analytical Differentiation of p-Tau 205 and p-Tau 212 

The p-Tau 205 and p-Tau 212 assays represent a significant advancement in tau biomarker science. Each assay targets biologically meaningful phosphorylation sites that are strongly associated with neuropathological staging and clinical decline. They demonstrate high analytical performance across multiple matrices: CSF, plasma, and serum, enabling wide applicability in diverse clinical and research settings. Importantly, both assays offer exceptional signal clarity and specificity, minimizing background noise and improving quantitation even at low concentrations. Developed in collaboration with academic partners and rigorously validated in multiple cohorts, these assays exemplify the precision and translational utility required for modern Alzheimer’s research. 

Translational Use Cases 

The expanded tau biomarker portfolio enables a diverse set of translational applications across the Alzheimer’s disease research and development continuum. In clinical trials, p-Tau 205 can serve as a valuable tool for stratifying patients based on neurofibrillary tangle burden and for monitoring therapeutic response to tau-targeted interventions. p-Tau 212, by contrast, supports early-stage detection strategies and enrollment optimization in prevention-focused trials, given its association with early and mid-phase pathology. When used alongside brain-derived tau (BD-Tau), p-Tau 212 may help identify individuals with CNS-specific tau pathology, providing critical insight into likely responders for disease-modifying therapies. Moreover, this expanded panel offers strong utility in large-scale, population-based studies, where longitudinal analysis of multiple tau biomarkers, such as p-Tau 217, p-Tau 205, and p-Tau 212, can help map disease trajectories and assess intervention impact across diverse cohorts. 

Enabling Therapeutic Discovery and Response Monitoring 

As tau-directed therapeutics continue to expand, from monoclonal antibodies to antisense oligonucleotides and kinase inhibitors, so too must the tools used to evaluate them. p-Tau 205 is particularly well-aligned with therapies targeting tau aggregation, given its association with advanced neurofibrillary pathology. In contrast, p-Tau 212 offers a window into earlier tau dysregulation, potentially reflecting changes in soluble tau species that are affected prior to structural tangle formation. Together, they provide a powerful pharmacodynamic toolset for clinical trial stratification, endpoint selection, and mechanistic insight. These assays can be used to enrich enrollment for those most likely to benefit, detect on-target engagement, and support regulatory filings with objective molecular measures of therapeutic effect. 

Versatility Across Study Designs and Populations 

The ability to quantify p-Tau 205 and p-Tau 212 across CSF, plasma, and serum expands their value in both cross-sectional and longitudinal study designs. This versatility allows them to be applied in highly controlled academic cohorts, global multi-site biobanks, or interventional studies without the need for matrix-specific revalidation. They are especially well-suited for use in NIH-supported cohorts where harmonized biomarkers are critical for multi-modal disease modeling. Their robustness also supports personalized trajectory mapping, biomarker-informed prognosis, and transition prediction from prodromal to symptomatic stages, key use cases in a field moving toward preventive treatment models. 

Commercial Availability and Implementation 

Both p-Tau 205 and p-Tau 212 assays will be commercially available from Quanterix and validated for use on the Simoa HD-X Analyzer® on July 1st. They are supported by standardized protocols, documentation, and technical validation reports to ease onboarding in academic, CRO, or pharma settings. The assays can be ordered individually, or pilot feasibility studies can be initiated through Quanterix’s Accelerator Lab. To learn how these new biomarkers can elevate your Alzheimer’s disease research, contact the Quanterix team to discuss implementation and study design support. 

Integrating Tau Biomarkers for Comprehensive Disease Profiling 

Quanterix’s expanded portfolio of tau biomarkers supports a modular framework that aligns specific analytes to disease phases, matrices, and use cases: 

Biomarker	Biological Phase	Matrix	Primary Utility
p-Tau 181	Early amyloid/tau cross-talk	CSF, plasma	Diagnostic, screening
p-Tau 217	Early to mid-stage progression	CSF, plasma	Stratification, staging
p-Tau 205	Late-stage tau tangle accumulation	CSF, serum, plasma	Disease severity, therapeutic response
p-Tau 212	Early to mid-stage progression	CSF, serum, plasma	Non-invasive monitoring, clinical trial endpoint
Total Tau	Global tau burden	CSF, plasma	Differentiation from other tauopathies
BD-Tau	CNS-specific tau signal	Plasma	High specificity for neurodegeneration

This multi-biomarker approach provides flexibility to adapt to varying research and clinical contexts, allowing for personalized strategy design in drug development, trial enrollment, and disease tracking. 

Simoa^® Technology: Enabling Ultra-Sensitive Tau Detection 

All assays in the Quanterix tau portfolio are developed on the ultra-sensitive Simoa platform, which enables quantification of low-abundance phosphorylated tau species in  CSF, serum, and plasma. Compared to conventional immunoassays, Simoa offers: 

• Sub-femtomolar sensitivity 
• Wide dynamic range for longitudinal tracking 
• Minimal background and high reproducibility 
• Validated performance across instruments and sites 

Conclusion: Charting the Future of Alzheimer’s Biomarker Science 

The future of Alzheimer’s biomarker science will be shaped not by a single breakthrough, but by the thoughtful integration of complementary tools, each offering a unique lens on the disease. With p-Tau 205 and p-Tau 212, Quanterix expands that lens, capturing new phases of tau pathology, unlocking peripheral monitoring capabilities, and supporting scalable clinical translation. 

Built on the high-sensitivity Simoa platform and integrated with a broader portfolio that includes p-Tau 181, p-Tau 217, total tau, and BD-Tau, these assays form the backbone of a future-ready diagnostic infrastructure. They empower researchers, clinicians, and drug developers to decode Alzheimer’s disease with greater clarity, and to move closer to interventions that are not just targeted, but truly personalized. 

References 

1. Ashton NJ, Montoliu-Gaya L, Benedet AL, et al. CSF p-tau205: a biomarker of tau pathology in Alzheimer’s disease. Acta Neuropathologica. 2024 Jan;147:12. https://doi.org/10.1007/s00401-023-02659-w 

2. Barthélemy NR, Saef B, Li Y, et al. CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease. Nature Aging. 2023 Apr;3:391–401. https://doi.org/10.1038/s43587-023-00380-7 

3. Lantero-Rodriguez J, Montoliu-Gaya L, Vrillon A, et al. A novel immunoassay for CSF p-tau205 and p-tau202 reveals strong associations with tau PET and cognitive decline in Alzheimer’s disease. Acta Neuropathologica. 2024;147:12. https://doi.org/10.1007/s00401-023-02659-w 

4. Kac PR, Alcolea D, Montoliu-Gaya L, et al. Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer’s disease. Alzheimer’s Dementia. 2025;21:e70172. https://doi.org/10.1002/alz.70172 

5. Kac PR, González-Ortiz F, Emeršič A, et al. Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology. Nature Communications. 2024;15:2615. https://doi.org/10.1038/s41467-024-46876-7 

6. Barthelemy NR, Li Y, Joseph-Mathurin N, et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Nature Medicine. 2020 Mar;26(3):398–407. https://doi.org/10.1038/s41591-020-0781-z 
   
7. Strain JF, Barthelemy NR, Horie K, et al. CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease. Neurobiology of Disease. 2022 Jun 15;168:105714. https://doi.org/10.1016/j.nbd.2022.105714