Before groundbreaking therapies for Alzheimer’s disease gained approval, the concept of biomarker tests remained on the periphery. However, a new dawn is breaking in the realm of Alzheimer’s treatment, with Eisai and Biogen’s anti-amyloid wonder drug, Leqembi, making its triumphant debut. Eli Lilly’s promising donanemab is poised for imminent approval, fueling a surge in Alzheimer’s drug development and an accompanying sprint in the race to devise efficient diagnostic tools.
With the resounding green light for Leqembi, the Centers for Medicare and Medicaid Services (CMS) have unfurled a broader coverage plan, albeit with certain prerequisites. Physicians now find themselves in the realm of qualified registries, while patients must bear the stamp of a diagnosis, presenting mild cognitive impairment or the early stages of Alzheimer’s disease with undeniable beta-amyloid deposits.
To pave the reimbursement path, CMS laid down a bold proposal in July 2023 – an expansive increase in coverage for PET scans, essential for pinpointing those elusive amyloid plaques. However, the quest for swifter, more affordable diagnostic methods continues unabated.
Over the last decade, the Alzheimer’s landscape has been teeming with the birth of biomarker tests, each one a potential game-changer. In June, the FDA greenlit two groundbreaking tests from Roche, capable of measuring the elusive beta-amyloid and tau proteins in the cerebrospinal fluid (CSF). And just at the close of July, Quest Diagnostics raised the curtain on a pioneering, direct-to-consumer blood-based biomarker test for Alzheimer’s, heralding a new era of accessibility.
In the words of Ted Wilson, an investigator with the Alzheimer’s Disease Research Center Biomarker Core at Stanford University, “It’s an electrifying era for Alzheimer’s biomarker research.” While these tests haven’t yet earned their stripes as full-on replacements for PET scans, the research community is harboring optimistic dreams of a future where they just might.
Diagnostic Challenges
n a nation where 6.7 million souls grapple with the shadow of Alzheimer’s disease, and that number only poised to surge, the price tag of dementia looms large over the United States in 2023, a staggering $345 billion. Yet, amid this pervasive reality, the quest for an accurate diagnosis remains a Herculean task.
The labyrinth of dementia is complex, with its various forms often weaving a web of overlapping cognitive symptoms. Amanda Heslegrave, a research fellow at the UK Dementia Research Institute Biomarker Factory, explains that Alzheimer’s, though dominant, shares the stage with formidable co-stars like frontotemporal and vascular dementia. Sometimes, patients grapple with multiple forms of dementia, creating a diagnostic puzzle that only finds its solution in the afterlife.
Ted Wilson, an investigator at the Alzheimer’s Disease Research Center Biomarker Core at Stanford University, remarks, “The complete truth about what’s happening in the brain often eludes us until it’s too late.”
Thus, the diagnosis of Alzheimer’s becomes a process of elimination, a painstaking journey of ruling out other potential culprits behind the veil of cognitive decline. M. Laura Parnas, the disease area network lead in cardiometabolism and neurology at Roche Diagnostics, notes that securing an accurate diagnosis can take years, years that patients and their families can ill afford.
For treatment decisions to hit the mark, precision is key. Take frontotemporal dementia, for instance, a condition that doesn’t typically feature the ominous buildup of amyloid plaques. In such cases, groundbreaking anti-amyloid therapies like Leqembi would miss the mark entirely.
To unravel this diagnostic enigma, a spotlight has fallen on biomarker tests. These remarkable assays often zero in on two culprits—amyloid and tau proteins—that gather in the brains of dementia sufferers. Another star player is neurofilament light chain (NfL), a marker of nerve cell degeneration. Elevated NfL levels signal swift neurodegeneration and disease progression, although a commercial diagnostic test utilizing this biomarker remains a tantalizing prospect.
So far, the approved tests target two bodily fluids: cerebrospinal fluid (CSF) and blood. CSF samples require a lumbar puncture, a procedure that patients seldom embrace with open arms. But the next frontier in Alzheimer’s diagnostics beckons: blood tests. These noninvasive biomarker tests could usher in a new era of affordability for patients and healthcare providers alike, offering a ray of hope.
Yet, the path to success is fraught with challenges. Alzheimer’s biomarkers in blood often exist in minute concentrations, obscured by other proteins that can muddy the diagnostic waters. Wilson reflects, “At first, it seemed like an insurmountable task to harness the power of plasma for detecting these elusive proteins.” But as science advances, hope endures, and the quest for a breakthrough continues.
Currently Available Alzheimer’s Tests
In the dynamic world of Alzheimer’s diagnostics, Roche Diagnostics stands as a pioneering trailblazer. Back in 2022, it marked a milestone by launching its Elecsys CSF beta-amyloid and phosphorylated-tau assays. And this June, the FDA bestowed its blessing upon Roche once more, granting clearance for the Elecsys CSF beta-amyloid and total tau assays.
These paired tests form a formidable duo, working in harmony to measure the delicate balance between beta-amyloid and tau proteins in the cerebrospinal fluid (CSF). Amanda Heslegrave explains that these tests serve as a window into the brain’s inner workings. When amyloid and tau levels in the CSF soar, it’s often a telltale sign of Alzheimer’s disease in action. On the other hand, an elevated concentration of tau alone may point to other dementia culprits behind the curtain of cognitive decline.
But Roche isn’t the sole player in this high-stakes diagnostic arena. Fujirebio Diagnostics made its mark in 2022 with a beta-amyloid CSF test gaining the FDA’s marketing nod. The CSF tests are no slouches when it comes to accuracy, with results on par with the gold standard—PET scans—for diagnosing Alzheimer’s disease.
For now, the Alzheimer’s Association advocates coupling these tests with PET scans to confirm the presence of those pesky amyloid plaques in the brain, thereby locking in an official Alzheimer’s diagnosis and the coveted ticket to Leqembi treatment. However, the Centers for Medicare and Medicaid Services (CMS) maintain an enigmatic stance on how the disease should be verified, leaving the diagnostic landscape shrouded in uncertainty.
Presently, biomarker assays mostly shine as stars on the clinical trial stage, screening patients and tracking the impact of experimental drugs, often partnered with comprehensive neuropsychological assessments and clinical observations, according to Ted Wilson.
But don’t blink; the future holds the promise of blood-based biomarker tests. Quest Diagnostics tantalized us with its July revelation of a blood-based test, though it stops short of being crowned an official Alzheimer’s diagnostic. Still, it provides valuable insights into the risk of Alzheimer’s disease.
C2N Diagnostics, too, marches forward with a blood-based Alzheimer’s test measuring plasma-tau and amyloid levels. Their second-generation marvel, PrecivityAD2, recently turned heads by matching the diagnostic precision of CSF tests and PET scans.
As M. Laura Parnas envisions, these blood-based tests could very well become the heralds of an official Alzheimer’s diagnosis, offering an affordable alternative to the regal imaging techniques like PET scans. The future is poised to transform the diagnostic landscape, making early detection and intervention more accessible than ever.