Roche scientist discusses recent progress in blood-based biomarkers and the future of Alzheimer’s diagnostics.
It is shaping up to be a big year for Alzheimer’s diagnostics, as blood-based biomarkers continue to demonstrate significant potential to change how the disease is detected. By providing a simpler alternative to the current standards for Alzheimer’s testing, it is hoped that blood tests will transform the diagnostic process by reducing the need for invasive and expensive diagnostic procedures, and ensuring timely access to appropriate care and emerging therapies.
At the recent Clinical Trials in Alzheimer’s Disease (CTAD) conference, Roche Diagnostics presented data demonstrating positive results from its pTau 181 test by itself or combined measurements of pTau181 and apolipoprotein (ApoE4) in blood plasma to rule out Alzheimer’s-related amyloid pathology. The company also presented data on its pTau217 assay, which demonstrated high accuracy in detecting amyloid pathology. Both tests have received FDA Breakthrough Device Designations.
As blood based biomarkers for Alzheimer’s are a topic of high interest in the field, will 2025 be the year that we finally see blood-based diagnostics become a new standard of care?
Longevity.Technology: With so many news stories in recent years highlighting the progress being made in blood tests for Alzheimer’s, it can be easy to forget that these technologies are still not yet standard practice in healthcare. Indeed, the FDA has yet to approve the use of any blood-based biomarkers for the disease. To learn more about where the field currently stands, and where it goes from here, we sat down with Maria-Magdalena Patru, MD, PhD, who leads the neurology medical team at Roche Diagnostics US.
Most of the excitement surrounding blood-based Alzheimer’s tests stems from their potential to address the accessibility and invasiveness issues associated with current diagnostic methods. While Dr Patru is keen to stress that the current FDA-approved tests for Alzheimer’s (positron emission tomography (PET) scans, and cerebrospinal fluid (CSF) assays are highly effective, she agrees there are limitations.
“PET has the advantage of being able to visualize and quantify, but it does have disadvantages when it comes to accessibility,” she says. “It’s not available everywhere, it is costly and comes with a certain degree of invasiveness.”
‘Excitement is justified’
Similarly, Dr Patru notes that the CSF biomarker assays, while also highly accurate, are perceived as more invasive due to the need for a lumbar puncture procedure. All of which is driving the race to develop and offer approved blood-based tests.
“The excitement around blood tests is justified, because the invasiveness is minimal – a blood draw is a much more routine procedure compared to a lumbar puncture,” she says. “The accessibility of blood tests is also significantly higher compared with that of PET scans.”
Despite the enthusiasm, Dr Patru acknowledges the challenges in developing accurate blood-based Alzheimer’s tests, and that the transition from measuring brain specific proteins in CSF to measuring them in blood is not a trivial matter.
“Analytically, you need to adjust to the blood matrix when you develop the blood-based assays,” she explains. “There are lower concentrations of these proteins in blood than in CSF, and that requires more sensitive tests.”
The neurology teams at Roche have been working to address these challenges.
“Clinically, you need to demonstrate the performance of the test in the intended use population. Therefore, we have been conducting a multi-site trial worldwide for the clinical validation of these plasma biomarkers,” says Dr Patru, referring to the study that provided the data presented recently at CTAD. “These are just part of the comprehensive development work that has to be done to demonstrate to the FDA, but also to our customers and patients, that the test is safe and effective.”
Approved tests this year?
When discussing the timeline for the availability of blood-based Alzheimer’s tests, Dr Patru is optimistic.
“With so many manufacturers working on developing these blood-based biomarkers, I think there is a high probability to see an approved test on the market in 2025,” she says. “If not, then in 2026 for sure.”
However, Dr Patru emphasizes the importance of understanding the intended use and performance of these first tests, as they may be validated and approved for different purposes, such as rule-out or confirmatory testing.
“People have to understand that a test which was validated in a certain population cannot be used in a different intended use population with similar results,” she says. “For example, a test approved for a symptomatic population if used in an asymptomatic population would be considered ‘off-label’ use and it is expected that the test performance will be different.”
Looking ahead, Dr Patru envisions a future where a panel of biomarkers, rather than a single test, will be used for comprehensive Alzheimer’s diagnosis.
“It’s almost never just about one biomarker for a disease, especially in Alzheimer’s, which has such a complex pathology,” she says. “Clinicians are going to need a panel of biomarkers, to aid in AD diagnosis and disease staging, but most importantly a panel that encompasses biomarkers for differential diagnosis with other causes of dementia.”
Diagnosis key to treatment
The widespread availability of accurate diagnostic tests is also going to be crucial for identifying patients in the early stages of Alzheimer’s disease, as this is when novel therapies are most effective.
“If you do not identify these patients, they are going to progress into dementia stages, and once they are in the moderate and severe dementia stages, these drugs are not going to be effective,” says Dr Patru, pointing out that pharmaceutical companies are also exploring therapies for the preclinical, asymptomatic stage of Alzheimer’s, where the pathology begins to accumulate before symptoms appear.
While blood-based testing can also potentially help catch Alzheimer’s in its asymptomatic phases, Dr Patru is also excited about the prospect of combining the approach with AI and digital biomarkers.
“There is a lot of work that is being done in developing a variety of digital biomarkers, which can expedite the cognitive assessment and be very sensitive,” she says. “It’s a very fast-evolving field, and things are being approached from multiple angles. I hope that in the future, there will be algorithms that can combine the result of a digital cognitive assessment with the result from a blood test and with other clinical findings to give the physician a more accurate and complete picture of a patient’s condition.”
Do better for patients
While addressing the Alzheimer’s disease in the asymptomatic stages is clearly the future of the field, Dr Patru also emphasizes the importance of focusing on the early symptomatic stages of the disease.
“We cannot miss the mild cognitive impairment stage, for example, because once a patient transitions into the dementia stage, then they lose the opportunity to have an effective treatment,” she says. “I think, until we have the right therapies and approach for asymptomatic individuals, we need to really focus on identifying early symptomatic patients. I’m also referring to the symptomatic patients that might not even present to the doctor, thinking that their symptoms are a normal part of aging. With the advancements in testing and therapies, there are a lot of things that can be done for those patients, and we need to be better at helping them.”
Dr Patru says that part of this is simply about education and awareness.
“At Roche, we have multiple educational programs to increase disease awareness, explaining the importance of early diagnosis and the current solutions to a better diagnosis, disease-specific treatment and improved patient outcomes. It’s important for all of us in the field of neurology – manufacturers, academia, and health care providers – to work together for the benefit of these patients.”
