Addressing the unmet need in Alzheimer’s diagnostics

March 21, 2025
 

As a pioneer in diagnostic development, Roche Diagnostics is committed to developing innovative biomarker tests that can help clinicians accurately diagnose neurological disorders and guide treatment. Roche Diagnostics is uniquely positioned to support better access to diagnostics through its broad footprint of testing platforms used in hospitals, clinics and other care settings worldwide.

With amyloid-targeting therapies now on the market and many more therapeutic solutions advancing through the clinical pipeline, accessible and effective tools for diagnosing and staging Alzheimer’s disease (AD) are more important than ever. In this Q&A, Maria-Magdalena Patru, M.D., Ph.D., scientific partner, CNS, and Margherita Carboni, Ph.D., indication lead, Neurology, discuss biomarker assay development at Roche Diagnostics and their perspectives on the evolving field of Alzheimer’s diagnostics. 

What excites you most about the future of Alzheimer’s disease diagnostics? 

Maria-Magdalena Patru, M.D., Ph.D. (MMP): The current availability of testing tools and amyloid-specific therapies and the promise for more. Especially in Alzheimer’s, the field is evolving very quickly – there are constantly new and exciting discoveries we consider in our development strategies as the pieces of this puzzle come together. The current availability of cerebrospinal fluid (CSF) and imaging biomarkers with their ability to detect amyloid pathology and qualify patients for amyloid targeting therapies has already transformed the way this disease is approached by clinicians. The patient pathway will be further streamlined once blood-based and digital biomarkers are validated and implemented in clinical practice.

However, the relatively specialized nature of AD testing and therapies poses its own limitations, as there’s a critical shortage of neurologists paired with a growing pipeline of patients. Our next big challenge is optimizing how these tools can be used together in both primary and specialty care settings to make diagnosis and treatment accessible for as many patients as possible. For example, in addition to clinical and cognitive assessments, ruling out symptomatic patients with a low likelihood of Alzheimer’s pathology with triage testing in primary care and referring the ones with positive results for further confirmatory testing in specialty care could translate into a faster, timely AD diagnosis and treatment and increased probability of positive outcomes. 
 

Margherita Carboni, Ph.D. (MC): I’m excited about the effect this progress will have on patients and their families. Alzheimer’s disease is uniquely challenging due to the stigma surrounding a diagnosis that isn’t visible. In contrast, when facing a disease like cancer, patients can often see a tumor on a scan and understand the cause of their symptoms. Biomarker tests can give patients clarity around an Alzheimer’s diagnosis, providing evidence of their disease and guiding potential treatment options. This has a massive impact on the quality of care patients receive. 

For example, one multicenter study found that almost one-third of patients presenting with mild cognitive impairment were misdiagnosed through clinical evaluation alone, and the addition of CSF biomarker test results modified management for 46% of cases.¹ As we identify more biomarkers and pharma companies work to develop therapies targeting specific pathologies, I think the field is moving closer to the goal of a precision medicine approach. When we can help patients get answers and provide routes to possible therapeutic options, it can really change lives.

Why is Alzheimer’s disease such an important area for diagnostics research and development?

MMP: Before the recent approval and introduction of biomarker tests and amyloid-targeting therapies, the field faced a critical lack of diagnostic tools and disease-specific treatment options. Identifying AD pathology with biomarker tests moves AD from a diagnosis of exclusion towards one of inclusion, increases diagnostic accuracy and qualifies patients for amyloid-targeting therapies shown to slow cognitive decline. These therapies are most effective in early-stage disease, so identifying patients in the initial symptomatic stages (such as mild cognitive impairment or mild dementia) is essential in ensuring that patients have a chance to receive timely treatment. 

Roche Diagnostics has made valuable progress in the field thus far by developing accessible, scalable and time-efficient tests: Two Elecsys CSF-based ratio assays of three different AD-relevant biomarkers ( pTau181/Amyloid beta42 and TotalTau/Abeta42) are currently cleared by the FDA and available to laboratories. These tests can detect amyloid pathology in early-stage symptomatic disease and aid clinicians in diagnosis and treatment decisions. Additionally, Roche’s pTau181 and pTau217 plasma biomarker tests* have received Breakthrough Device Designation, highlighting strides forward in developing blood-based AD biomarker assays and their potential for broadening access to timely and accurate diagnosis. 

AD is a complex disease with multiple pathologies, so we must continue working to ensure that patients have the right test for their clinical needs – not just for now, but also for the future when more therapies become available.
 

How does your team identify potential Alzheimer’s disease biomarkers for assay development? 

MC: At the highest level, we consider the process in two phases: biomarker identification and biomarker development. For biomarker identification, our primary focus is staying close with researchers in the field and staying on top of scientific advances. Historically, our biomarker research and diagnostic development has been highly collaborative with leading academics and pharma companies worldwide working to develop novel diagnostics and supportive assays for disease-modifying therapies.

Many factors then shape the decision to develop biomarker assays for clinical use. Here, we’re not necessarily starting with a specific biomarker and seeing what it can do. Instead, we look at unmet clinical needs and consider which biomarker can best accomplish those goals. We need to understand a biomarker’s intended use in a given population and work to validate prototype assays. Performance is key here – if we don’t have an assay that performs well, we don’t have a product. And then there’s the real-world utility of the biomarker. Is there interest in the test, and would it be clinically and technically feasible? I think at Roche, one of our greatest strengths is biomarker development and translating the latest discoveries into accurate, well-validated tests that can be used reliably around the world. Our platforms have a massive footprint – for example, we have more than 4,000 immunoassay instruments installed in the U.S. with more being added every day, making Roche assays broadly accessible.

What is the typical development timeline for a new diagnostic reaching the market? 

MC: It really depends. Internally, strong relationships with industry leaders, academic experts, patient advocates and pharma partners can guide decisions about what is most promising for clinical practice and what to prioritize. When a potential assay is recognized as a particularly valuable medical solution, there’s more effort to try to accelerate development timelines. However, the entire process is dependent on interactions with regulatory authorities as well as the extent of clinical validation necessary for a diagnostic to gain approval. We can have a strong base of analytical validation evidence that confirms a test’s technical performance, but that must be followed up with evidence that the test also provides accurate, clinically meaningful insights in a real-world setting. Products may require full prospective data collection through new, dedicated clinical studies, which require a great deal of time and resources. But in some cases, they can be retrospectively validated against a standard of care using existing clinical data.
 

What steps does Roche take to achieve consistent, reliable assay results, and why is this a top priority?

MC: One of the most valuable aspects is standardization. We want to know that, regardless of where a patient is tested, the results will be reliable and accurate. When we develop an assay for use with Roche instrumentation, we can be confident that every instrument is performing consistently and can rely on the same cut-off values for a test performed anywhere in the world. 

MMP: We develop tests for patients and with patients’ needs in mind, and we know that the reliability of results is key to making good clinical decisions. Therefore, every single step of assay design and development is aligned with this goal. Analytically, we strive to calibrate the assay to available reference materials to establish the accuracy of results. The precision of the assay is also tested on multiple instruments and in different conditions to ensure that, regardless of where the test will be performed, the results will not vary significantly. The reagent lots have certain acceptance criteria for release to ensure lot-to-lot consistency of the results. 

We also perform extensive clinical validation of these tests in the intended use population to demonstrate safety and efficacy. Especially in neurology, where the standard of care is now undergoing significant changes, having a reliable test from the beginning is key to gaining the confidence of laboratorians, clinicians and patients and to ensuring its adoption and implementation in clinical practice. 

References

1. Cognat E. et al., BMJ Open. 2019 May 30;9(5):e026380. doi: 10.1136/bmjopen-2018-026380.