| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
Diagnostic ecosystem boosts access to timely Alzheimer's disease testing
Eye on Innovation
Alzheimer's disease takes a terrible and growing toll. In the United States alone, 6.7 million individuals aged 65 and older live with the disease. That number is projected to climb to 7.2 million by 2030, and 13.8 million by 2060. In addition to the distress experienced by patients and their families, the financial impact of Alzheimer's disease is also rising. Healthcare costs associated with Alzheimer's care in the United States are expected to reach $1 trillion by 2050.
Fortunately, progress is being made. There's no cure yet. But greater understanding of the disease has led to new diagnostic tools and medications targeting beta amyloid plaques, a hallmark of Alzheimer's. The availability of these disease-modifying therapies underlines the importance of early and accurate diagnosis.
"For patients to have access to these drugs, the presence of amyloid pathology first needs to be demonstrated," says Alicia Algeciras-Schimnich, Ph.D., co-director of the Clinical Immunoassay Laboratory in the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota.
Mayo Clinic Laboratories has developed a cutting-edge suite of Alzheimer's disease testing. The newest assays use blood samples, avoiding the need for lumbar punctures to obtain cerebrospinal fluid. The portfolio includes an immunoassay for p-Tau217 that was developed in-house. It also includes C2N Diagnostics’ family of Precivity™ blood tests, which aid the detection of Alzheimer's pathology in symptomatic patients aged 55 and older.
The Alzheimer's disease testing suite exemplifies Mayo Clinic Laboratories' innovative business approach. As a platform company, Mayo Clinic is creating a diagnostics ecosystem to meet a wide range of testing needs.
"Now that we have disease-modifying therapies available, biomarker testing for Alzheimer's disease will become an essential component of the clinical evaluations of patients with cognitive impairment," Dr. Algeciras-Schimnich says. "Introducing Alzheimer's disease blood biomarkers into clinical practice provides noninvasive, rapid, cost-effective, and easily accessible tools for clinicians and patients."
The average age of diagnosis for people with Alzheimer's disease is 65. Early in the disease process, individuals often develop mild cognitive impairment (MCI). At that stage, low-level changes in memory, cognition, and conversational ability might not interfere with daily life. But one-third of people with MCI due to Alzheimer's develop dementia within five years.
Identifying Alzheimer's disease at the onset of MCI opens a window of opportunity for disease management. Symptom progression can be slowed not only through medication but also with healthy lifestyle habits that have been shown to improve cognitive function.
Definitive diagnosis of Alzheimer's disease requires post-mortem identification of beta amyloid plaques in the brain. Physicians treating patients must rely on advanced brain imaging and plaque biomarker testing. For decades, standard biomarker testing required cerebrospinal fluid. The discovery that blood biomarkers also can identify Alzheimer's disease pathology propelled the development of plasma-based testing.
"Blood biomarkers are a noninvasive and scalable tool," Dr. Algeciras-Schimnich says. "With a simple blood draw, patients can have access to timely diagnosis."
Mayo Clinic Laboratories' new plasma biomarker assay (Mayo ID: PT217) uses p-Tau217 protein to identify amyloid beta pathology in symptomatic individuals aged 50 and older. The assay isn't intended as a screening test for asymptomatic people. Test results are available in one to five days.
To boost the accuracy of reported test results, PT217 uses a two-cutpoint approach. "It's a relatively new concept in laboratory medicine," Dr. Algeciras-Schimnich says.
Below a specific level or cutpoint, PT217 test results are considered negative for amyloid beta pathology. Results above a second, higher cutpoint are deemed positive. Test results between the two cutpoints are classified as intermediate. The assay's cutpoints have been optimized to provide a sensitivity of 92% and specificity of 96% for the detection of abnormal amyloid pathology.
"We wanted to make sure that when we classify a result as positive or negative, we are very certain that amyloid beta pathology indeed is or is not present," Dr. Algeciras-Schimnich says. "The two-cutpoint approach maximizes the overall test accuracy for individuals with a positive or negative result and minimizes the number of patients who will need additional testing for confirmation of amyloid pathology."
One of the challenges of introducing Alzheimer's disease blood biomarkers into clinical practice is the difference in clinical performance of various blood biomarkers and even of various assays for the same biomarker. To overcome such challenges, Mayo Clinic Laboratories routinely partners with Mayo Clinic physicians.
"Before selecting our p-Tau217 testing, we performed a clinical validation of various assays, in collaboration with the behavioral neurology practice," Dr. Algeciras-Schimnich says. The sample cohort was drawn from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. That research affirmed the utility of a two-cutpoint approach and guided the choice of a specific PT217 assay.
"As part of our analytical validation, we found that p-Tau217 is a very stable biomarker in plasma," Dr. Algeciras-Schimnich says. "This allows clients to send the sample to us refrigerated, with no need for special sample collection or processing."
The Precivity blood tests (Mayo ID: C2NAD and C2AD2) simultaneously quantify plasma amyloid beta concentrations and determine the presence of APOE-specific peptides. The APOE gene is linked to an increased risk for Alzheimer's disease. Research found that the Precivity AD2 test delivered accuracy of over 90% in both primary care and specialty care settings compared with CSF or amyloid PET analysis. That result was validated despite a relatively high rate of medical comorbidities — such as cardiovascular and kidney disease — among patients in the study cohort.
"We have compelling evidence that our platform is among the most robust testing options available," says Joel B. Braunstein, M.D., MBA, co-founder and chief executive officer of C2N Diagnostics. "Achieving a level of performance on par with CSF and PET amyloid testing is a major innovation for the field and for patient care."
Plasma biomarker innovations might eventually help overcome disparities in healthcare access. Professional and clinical organizations haven't yet endorsed plasma testing for Alzheimer's disease in primary care settings. But compared with CSF or PET, plasma testing could be easier to implement in those settings.
"Many patients don't see a specialist for their memory care. Primary care providers are the main gatekeepers," Dr. Braunstein says. "We also know that about 15% of patients are ineligible for lumbar puncture because of bleeding risks, and that 60 million Americans don't live anywhere near a specialized facility with access to PET."
Recognizing the importance of precise diagnosis represents another paradigm shift. "For decades, there's been a general perspective that perhaps the specificity of a dementia diagnosis isn't absolutely critical. There's no cure, and a diagnosis can carry with it social stigma," Dr. Braunstein says. "But with the advent of online information, people want to be more proactive about their health. The informed consumer is always a more satisfied patient who can work best with their healthcare team."
Meeting the needs of patients is the cornerstone of test development at both Mayo Clinic Laboratories and C2N Diagnostics. The process involves identifying an unmet clinical necessity, innovating a solution, and rigorously testing that solution.
"Mayo Clinic Laboratories has a strong clinical mindset and places a high premium on quality that is quite special within the lab industry," Dr. Braunstein says. "That compatibility is why we chose to partner with Mayo."
"Our goal at Mayo Clinic Laboratories is to provide fast, accurate, and reliable answers to patients," Dr. Algeciras-Schimnich says. "It's an exciting time because the field is evolving very rapidly. Having rapid and scalable tools for the detection of amyloid pathology promotes equity in dementia diagnosis and treatment."
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