Introduction

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, affects millions of individuals worldwide. Early and accurate diagnosis is crucial for effective treatment and management of the disease. In recent years, researchers have made significant strides in identifying biomarkers that can aid in the early detection and monitoring of AD. One such promising biomarker is p-Tau 217, a specific isoform of tau protein phosphorylated at the 217 residue.

The Role of p-Tau 217 as a Biomarker for Alzheimer’s Disease

Accurate diagnosis of AD has historically relied on clinical assessments in combination with cerebrospinal fluid (CSF) biomarker measurements and neuroimaging techniques such as positron emission tomography (PET). However, these methods can be invasive, expensive, inaccessible, and may not be suitable for large-scale applications. The measurement of blood-based biomarkers offers a simple, cost-effective, accessible, and scalable approach to AD research, diagnosis, and progression monitoring.

Tau is a microtubule-associated protein important for neuronal stability. One of the major neuropathological hallmarks of Alzheimer’s disease (AD) is the hyperphosphorylation of the tau protein which is thought to lead to pathological tau spread and neuronal death. Recent, research studies have shown that plasma levels of p-Tau 217 are elevated in AD patients^1,2. Additionally, it has been demonstrated that plasma p-Tau 217 levels are increased in the early stages of the AD continuum and are correlated with amyloid-PET positivity^3-6. These findings suggest that p-Tau 217 may serve as a promising blood-based biomarker to aid in AD research, drug development, diagnosis, disease monitoring and patient care.

Potential Applications of p-Tau217 as a Blood-Based Biomarker Associated with AD

The use of p-Tau217 as a blood-based biomarker associated with AD shows great potential to be utilized in several important applications:

Clinical Trials and Drug Development: Blood biomarkers like p-Tau 217 have started to play a crucial role in AD clinical trials and drug development^7,8. The inclusion of blood p-Tau 217 measurements as an outcome measure can help assess the effectiveness of potential disease-modifying treatments, identify suitable participants for clinical trials, and monitor treatment response.

Early Detection: Early diagnosis of AD is crucial for timely intervention and improved patient outcomes. By measuring blood p-Tau 217 levels, healthcare professionals may be able to identify individuals at risk of developing AD during the onset of symptoms. Early detection can enable early intervention and the implementation of appropriate therapeutic strategies.

Differential Diagnosis: Distinguishing AD from other forms of dementia can be challenging, particularly in the early stages. Blood p-Tau 217 levels may aid in differentiating AD from other types of dementia, resulting in more accurate and timely diagnoses.

Disease Progression Monitoring: Tracking the progression of AD is essential for adjusting treatment plans and assessing therapeutic efficacy. Blood p-Tau 217 levels could serve as a tool to help measure disease progression, allowing healthcare providers to monitor changes over time and make informed decisions regarding patient care.

To learn more about p-Tau 217 at AAIC, please check out the following presentations and posters:

p-Tau 217 Presentations:

Plasma ALZPath p-tau217 for the identification of amyloid and tau positivity

Tuesday, July 18, 2:25 to 2:35pm Hall 2

p-Tau 217 Posters:

SUNDAY

• Plasma p-tau231 and ptau217 provides information on tau tangle deposition in symptomatic Alzheimer’s disease individuals
  Sunday July 16, 8:45 8:45 am to 4:15 pm P1-040

 
MONDAY 

• Plasma pTau217 single versus multiple phospho-site assay
  Monday, July 17 (CEST) 8:45 am to 4:15 pm P2-941
• Performance of optimized prototype LUMIPULSE G Immunoassays for plasma pTau181 and pTau217 
  Monday, July 17 (CEST) 8:45 am to 4:15 pm P2-939

TUESDAY

• ALZPath Dx:  A novel accessible, validated, and scalable phosphorylated – tau217 (ptau217) assay in blood
  Tuesday; July 18 (CEST) 8:45 am- 4:15 pm P3-266

WEDNESDAY

• Performance of plasma pTAU181 and pTAU217 measured with fully automated LUMIPULSE G Prototype immunoassays
  Wednesday, July 19 (CEST) 8:45 am- 4:15 pm P4-281
• The AppNL-G-F/MAPT mouse model of Alzheimer’s Disease demonstrates increased levels of ptau217 in CSF, changes that correlate with increased cerebral p-tau depositions
  Wednesday, July 19 (CEST) 8:45 am – 4:15 pm P4-073

• Plasma pTAU217 and NfL concentrations across diagnosis in an unselected memory clinic cohort
  Wednesday, July 19 (CEST) 8:45 am – 4:15 pm P4-282

References

1. Fossati S, Ramos Cejudo J, Debure L, et al. Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer’s disease. Alzheimers Dement (Amst). 2019;11:483-492. Published 2019 Jun 28. doi:10.1016/j.dadm.2019.05.001

2. Zetterberg H, Wilson D, Andreasson U, et al. Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther. 2013;5(2):9. Published 2013 Mar 28. doi:10.1186/alzrt163

3. Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA. 2020;324(8):772-781. doi:10.1001/jama.2020.12134

4. Mattsson-Carlgren N, Janelidze S, Palmqvist S, et al. Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease. Brain. 2020;143(11):3234-3241. doi:10.1093/brain/awaa286

5. Janelidze S, Berron D, Smith R, et al. Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease. JAMA Neurol. 2021;78(2):149-156. doi:10.1001/jamaneurol.2020.4201

6. Bayoumy S, Verberk IMW, den Dulk B, et al. Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231. Alzheimers Res Ther. 2021;13(1):198. Published 2021 Dec 4. doi:10.1186/s13195-021-00939-9

7. Pontecorvo MJ, Lu M, Burnham SC, et al. Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA Neurol. 2022;79(12):1250-1259. doi:10.1001/jamaneurol.2022.3392

8. Gueorguieva I, Willis BA, Chua L, et al. Donanemab exposure and efficacy relationship using modeling in Alzheimer’s disease. Alzheimers Dement (N Y). 2023;9(2):e12404. Published 2023 Jun 28. doi:10.1002/trc2.12404