Clinical Insights

MLM’s CSF and Blood Biomarker Capabilities for the Early Detection of Alzheimer’s Disease

MLM has 30 years of expertise in providing comprehensive central/specialty lab support for complex global clinical trials such as Alzheimer’s Disease.

The following neurodegeneration biomarkers are available within our laboratory network.

*MLM also supports qualification and validation of additional exploratory assays. 

Overview of Biomarkers in Alzheimer’s Disease 

Biomarkers are measurable indicators of a biological condition. In Alzheimer’s disease, biomarkers can be detected in cerebrospinal fluid (CSF), blood, or through imaging techniques. They reflect pathological changes in the brain, such as the accumulation of amyloid-beta (Aβ) plaques, tau tangles, and neurodegeneration.

Cerebrospinal Fluid (CSF) Biomarkers

CSF is a clear fluid that surrounds the brain and spinal cord, providing a window into brain pathology. The most established CSF biomarkers for Alzheimer’s disease include:

• Amyloid-beta 42 (Aβ42): A peptide that aggregates to form amyloid plaques, a hallmark of AD. Decreased levels of Aβ42 in CSF are indicative of plaque formation in the brain.
• Total Tau (t-tau): A protein associated with neuronal damage and death. Elevated levels of t-tau in CSF suggest neurodegeneration.
• Phosphorylated Tau (p-tau): A specific form of tau protein associated with tau tangles in the brain. Increased p-tau levels in CSF are linked to AD-specific neurofibrillary tangles.

Blood Biomarkers

Recent advances have identified blood-based biomarkers as a promising alternative for AD detection. Key blood biomarkers include:

• • Plasma Tau (p-tau181, p-tau217, p-tau231): These forms of tau, when elevated in blood, are associated with tau pathology in AD.
  • Neurofilament Light Chain (NfL): A marker of neurodegeneration, increased NfL levels in blood are correlated with axonal damage and neuronal loss.

Application in Clinical Trials

Biomarkers are critical in clinical trials for Alzheimer’s disease, serving multiple roles:

• • Participant Selection: Biomarkers can identify individuals at high risk for AD, allowing for the selection of participants who are likely to benefit from investigational treatments.
  • Disease Monitoring: Biomarkers enable the tracking of disease progression and the effectiveness of interventions over time.
  • Surrogate Endpoints: In some trials, biomarkers are used as surrogate endpoints, providing early indications of treatment efficacy before clinical symptoms change.

Plasma p-tau217

Recent research has highlighted plasma phosphorylated tau 217 (p-tau217) as a highly promising biomarker for Alzheimer’s disease. Compared to other tau biomarkers, p-tau217 in blood has shown remarkable sensitivity and specificity for detecting Alzheimer’s pathology, even in the early stages.

Recent Data on Plasma p-tau217

1. Sensitivity and Specificity:

• High Accuracy in Differentiation: Plasma p-tau217 has demonstrated the ability to distinguish Alzheimer’s disease from other neurodegenerative disorders with high accuracy. Studies have shown that p-tau217 can differentiate AD from non-AD dementias more effectively than other tau isoforms like p-tau181.
• Correlation with Amyloid and Tau Pathology: Plasma p-tau217 levels strongly correlate with amyloid-beta plaque deposition and tau tangles in the brain, as confirmed by PET imaging and CSF biomarkers. This makes it a reliable indicator of AD-related pathology.

2. Early Detection:

• Preclinical and Early Stages: Plasma p-tau217 can detect Alzheimer’s pathology even before the onset of significant cognitive symptoms, making it a valuable tool for identifying individuals in the preclinical or prodromal stages of AD.

3. Clinical Utility:

• Non-Invasive and Scalable: As a blood-based biomarker, p-tau217 offers a non-invasive, easily accessible, and scalable option for clinical trials and routine clinical practice. Its use could facilitate broader screening efforts and more personalized treatment strategies.

4. Comparison with Other Biomarkers:

• Superior Performance: In head-to-head comparisons with other plasma biomarkers like p-tau181, Aβ42/Aβ40 ratio, and neurofilament light chain (NfL), p-tau217 has consistently shown superior performance in identifying Alzheimer’s disease.

Plasma p-tau217 :  Application in Clinical Trials

Given its promising characteristics, plasma p-tau217 is increasingly being incorporated into clinical trial designs. It is used for:

• Screening and Enrolling Participants: p-tau217 is employed to select participants with early or asymptomatic Alzheimer’s pathology, ensuring that trials target the right population.
• Monitoring Disease Progression: p-tau217 levels can track disease progression over time, offering a dynamic tool for evaluating the efficacy of therapeutic interventions.
• Potential as a Surrogate Endpoint: With further validation, p-tau217 could serve as a surrogate endpoint in clinical trials, providing early indications of treatment effects before cognitive decline becomes apparent.

Here’s the Long Story Made Short … 

Recent data underscores the potential of plasma p-tau217 as the most promising blood biomarker for Alzheimer’s disease. Its high sensitivity and specificity, coupled with the ease of blood sampling, make it a valuable asset in both clinical research and practice. As the field continues to evolve, p-tau217 is likely to play a pivotal role in advancing the early detection and treatment of Alzheimer’s disease.

For further reading on the role of p-tau217 in AD detection and therapeutic discovery, READ HERE.

Reach out to our team today to learn how our capabilities, magnified by our team’s agility and flexibility, can accelerate your therapeutic discovery projects in Alzheimer’s research >> CONTACT AN  MLM PROFESSIONAL