OSP: Could you explain how the LucentAD test works including how clinicians will benefit from using it?
MT: Sure, it is a simple blood test to determine if an individual is likely or not to have amyloid pathology consistent with Alzheimer’s disease. A standard blood draw is used to take a sample of a patient’s blood. The test can be ordered through a secure on-line portal, and then the blood sample is shipped to Lucent Diagnostics for processing. The result will be reported to the relevant physician within 10 days after it’s been received, and a notification is provided when the result is available.
The test is designed as a ‘rule out’ test. So, a negative result (below the cutoff) indicates a low likelihood of the presence of amyloid pathology and that alternative causes for the patient’s memory concerns should be investigated. A positive result (above the cutoff) is consistent with the presence of amyloid pathology and that additional confirmatory testing may be indicated for a diagnosis.
The aim is to provides a straightforward and convenient way for physicians to assess a patient’s likelihood of having amyloid pathology to complement other clinical assessments, including cognitive tests.
OSP: How do you see this speeding up the process – and how was the test discovered?
MT: The way it can simplify clinical workflows by reducing the number of unnecessary PET scans or spinal taps for CSF biomarker measurements to confirm amyloid pathology status. Additionally, it has the potential to reduce bottlenecks so that clinicians and patients can get answers faster.
The test measures a form of phosphorylated Tau (p-Tau181) in human plasma, which is associated with amyloid pathology, a hallmark of Alzheimer’s disease. Extensive clinical research supported by multiple peer-reviewed publications have validated the association of phosphorylated Tau in plasma with amyloid pathology. Several landmark studies spanning multiple independent cohorts and powered by the ultra-sensitivity of Quanterix’s Simoa platform demonstrated the specificity and accuracy of p-Tau181 for amyloid pathology in Alzheimer’s disease.
OSP: How exactly do you assess the likelihood of someone having amyloid pathology - what shows up - and can it indicate the likelihood of any other diseases?
LucentAD measures the concentration of p-Tau181 in plasma. The test performance was characterized by comparing plasma p-Tau181 concentrations with amyloid PET status in a large cohort of individuals with mild cognitive impairment. The test was optimized to maximize the clinical sensitivity and negative predictive value. To validate the cutoff, the test was performed on 293 patients from different clinical sites who were diagnosed with mild cognitive impairment based on clinical and cognitive assessments. LucentAD test demonstrated a clinical sensitivity of 90% and a specificity of 56%. The prevalence of amyloid positivity in this cohort was 34.5%. At this prevalence, the negative predictive value of the test was determined to be 91.4%.
OSP: Who are the targets for early screening, or do you believe everyone regardless of history should have early screening?
MT: It is intended for patients who are being evaluated for Alzheimer’s disease risk to aid in diagnostic evaluation. The test has been most extensively validated for individuals with mild cognitive impairment or early stage disease.
A physician needs to decide who is appropriate for LucentAD based on their clinical assessment and judgement.
OSP: What makes you sure they will become standard practice – is there anything that could stand in the way?
MT: There is a strong body of evidence supporting the validity of blood-based biomarkers for assessing Alzheimer’s disease pathology. This includes results from large clinical trials demonstrating the efficacy of new Alzheimer’s treatments. For example, measurements of p-Tau181 obtained using Quanterix’s platform are included on Eisai’s Leqembi label.
In addition to that, the National Institute of Aging in collaboration with the Alzheimer’s Association recently presented draft guidelines for the classification of Alzheimer’s disease using imaging and fluid biomarkers. Blood based biomarkers are included in the guidelines alongside other fluid biomarkers such as those measured in CSF. These guidelines are expected to be finalized and published in the coming months.
These developments are a reflection of advances in the performance and validation of blood biomarker assays and provide confidence that blood biomarkers for Alzheimer’s will gain adoption in clinical practice.