A flurry of news for Alzheimer diagnostics, and we're closing in on the international Alzheimer conference in Toronto, AAIC-26.
Two longstanding organizations, the Michael J Fox Foundation [Parkinson's] and te Alzheimer Drug Discovery Foundation, ADDF, are partnering, initially with $5M, to develop noninvasive testing. This $5M is part of a broader $50M effort of the ADDF to advance "next generation tests." 360Dx here on the $5M project, Precision Medicine Online here in March on the $50M project.
See an article in Science, 12 May 2026, writing
- Most dementia patients have multiple brain diseases.
- How should they be treated?
- Growing awareness of “copathology” inspires new diagnostic tests and clinical trials.
- See SIDEBAR 2, below.
Amprion Dx receives funding from Decathlon Partners as growth capital for both Parkinson's and Alzheimer's biomarkers. Here.
Anthem issues coverage for C2N multimodal PrecivityAD2 blood test. Press.
See the actual Anthem policy, Testing for biochemical markers in Alzheimer's disease, here: LAB.00046. Anthem provides policy for more general coverage for FDA-approved p217 tau tests. See SIDEBAR 1 below. It looks like the effective date for new Alzheimer coverage is October 1.
Three open access reviews, discusssed as SIDEBAR 3 below. See a 2025 narrative review of the field by Scholl here. See a 2025 Viewpoint from Wisch & Ances here. See a 2025 specific to plasma pTau by Teunissen et al here.
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AI CORNER (Chat GPT)
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Viewpoint on the News:
Blood Biomarkers Advance as Payer Policies Evolve
One way to read this week's news is against the backdrop of Medicare's decade-long evolution on amyloid PET imaging.
In 2013, CMS adopted one of its most restrictive coverage policies for any diagnostic technology, limiting amyloid PET almost entirely to Coverage with Evidence Development studies. The resulting IDEAS study, led by investigators at UCSF, demonstrated that PET frequently changed physicians' diagnoses and management plans but did not achieve its harder endpoint of reducing hospitalizations or emergency department visits. Nevertheless, much of the public messaging emphasized the management changes, while the more clinically important utilization results received less attention.
The landscape looks very different today. Anti-amyloid therapies have transformed biomarkers from primarily diagnostic tools into treatment-selection tools. In 2023, CMS withdrew its National Coverage Determination for amyloid PET altogether, leaving coverage decisions to the Medicare Administrative Contractors. Ironically, Medicare moved from one of its most tightly controlled diagnostic policies to one with remarkably little published contractor guidance.
Against that backdrop, Anthem's new medical policy is noteworthy. Rather than simply embracing every new blood test, Anthem has articulated a detailed clinical framework for both cerebrospinal fluid biomarkers and blood-based biomarkers. Blood tests are covered only in symptomatic patients after a standard diagnostic evaluation and only when results are expected to influence clinical management. The policy also recognizes FDA-cleared plasma assays as well as validated p-tau217 methodologies and explicitly positions blood testing as a triage tool that may reduce the need for PET imaging or lumbar puncture in selected patients.
Perhaps the greatest irony is institutional. Medicare currently has almost no publicly articulated coverage framework for amyloid PET beyond its general "reasonable and necessary" authority, while Anthem has published a detailed 20-page policy describing how blood biomarkers, CSF biomarkers, and PET imaging fit together in modern Alzheimer's diagnosis.
- Twenty years ago, observers might have expected Medicare to provide the more explicit national framework.
- In 2026, at least in this area, the commercial payer has become the more transparent rule-maker.
Taken together, the Medicare and Anthem stories illustrate how rapidly Alzheimer's diagnostics are evolving. A decade ago, the central reimbursement question was whether amyloid biomarkers should be covered at all. Today, the question has shifted to which biomarker should be used first, in which patients, and when more expensive confirmatory testing can safely be avoided.
Sidebar 1:
What Anthem's New Alzheimer's Biomarker Policy Covers
Anthem's revised medical policy (LAB.00046), effective October 1, 2026, creates a structured coverage pathway for both cerebrospinal fluid (CSF) biomarkers and blood-based biomarkers in the evaluation of suspected Alzheimer's disease. Unlike a product-specific coverage decision, the policy establishes clinical criteria that apply across technologies.
General eligibility requirements
Coverage begins with three overarching requirements:
The patient must have measurable mild cognitive impairment or dementia consistent with possible Alzheimer's disease, with an insidious, progressive course.
A standard diagnostic evaluation must already have been completed, including history and neurological examination, cognitive testing, and evaluation for reversible causes such as vitamin B12 deficiency, thyroid disease, depression, or medication effects.
The biomarker result must be expected to influence clinical management—for example, distinguishing Alzheimer's disease from other dementias, resolving conflicting clinical information, increasing diagnostic confidence, or determining eligibility for amyloid-targeting therapy.
CSF biomarkers
Coverage includes established cerebrospinal fluid biomarkers, including:
Aβ42 or the Aβ42/Aβ40 ratio;
phosphorylated tau (p-tau181 or p-tau217);
total tau; and
tau/amyloid ratio combinations.
Blood-based biomarkers
Blood testing is covered when:
the patient is age 50 years or older;
the assay is FDA-cleared or FDA-approved, or measures p-tau217 (or %p-tau217); and
testing is used to:
triage whether PET imaging or CSF testing is needed;
substitute for CSF when lumbar puncture is impractical or contraindicated; or
assist referral and specialty evaluation.
What is not covered
The policy excludes:
testing asymptomatic individuals, including those tested solely because of family history;
testing when another diagnosis already explains the cognitive impairment; and
repeat testing that is unlikely to change management.
How Anthem views blood tests
The policy stops short of treating blood biomarkers as universal replacements for PET or CSF. Instead, it describes them as clinically useful tools within a broader diagnostic pathway. The accompanying evidence review repeatedly notes that positive blood-test results may still require confirmation by PET imaging or CSF analysis, while negative tests may reduce the need for further evaluation in appropriate patients. It also notes that confirmation of amyloid pathology remains important when considering anti-amyloid therapies.
Overall, Anthem's approach reflects the direction increasingly advocated by Alzheimer's specialists: blood biomarkers become the first step in a staged diagnostic algorithm, while PET and CSF remain the reference standards for selected patients and high-stakes treatment decisions.
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SIDEBAR 2:
The SCIENCE article on Co-Pathology
Copathology: Dementia increasingly looks less like a set of cleanly separated diseases and more like overlapping mixtures of abnormal proteins. Autopsy studies show that many patients diagnosed with Alzheimer’s also have alpha-synuclein, TDP-43, vascular injury, or other pathologies, while many Parkinson’s patients with dementia also harbor amyloid and tau.
These combinations may help explain why symptoms, biomarker results, rates of decline, and treatment responses often fail to line up neatly. Researchers are therefore developing blood and spinal-fluid tests that measure several pathologies at once, rather than asking only whether a patient is “amyloid positive.” The immediate clinical problem is that diagnostics are advancing faster than treatment: physicians may soon be able to describe a patient as having a particular mixture of Alzheimer, Lewy body, vascular, and TDP-43 disease, while having drugs for only one component.
An upcoming donanemab trial in patients with both Lewy body dementia and high amyloid will test whether treating one pathology can still help in a mixed disease state.
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Nerd Note: PAMA
ACLA and others introduced general Category I biomarkers for Alzheimer's disease over the last 3 years. Most or all of these will be up for re-pricing under PAMA this summer.
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A short take on Wisch, Scholl, Teunissen reviews, as cited above.
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SIDEBAR 3:
Three Recent Reviews on Plasma Alzheimer's Biomarkers: Where the Field Stands
Three recent review articles reach remarkably similar conclusions: plasma biomarkers—particularly phosphorylated tau-217 (p-tau217)—are ready to transform the diagnostic pathway for Alzheimer's disease, although important issues of standardization, assay selection, and clinical implementation remain. Together, the papers portray a field moving rapidly from research into routine clinical practice.
Wisch provides the most concise clinical overview, written immediately after FDA approval of the first blood-based Alzheimer's assay (Lumipulse G pTau217/Aβ42 ratio). The authors emphasize that blood biomarkers should not be viewed as replacing clinical evaluation but rather as substantially improving diagnostic accuracy while expanding access beyond specialty memory clinics. They note that p-tau217 has emerged as perhaps the strongest individual plasma biomarker because it rises early in response to amyloid pathology and demonstrates excellent negative predictive value for ruling out Alzheimer's disease. They also stress that approximately one in five patients will have indeterminate results requiring follow-up PET or CSF testing, making plasma biomarkers best viewed as the first step in a staged diagnostic algorithm rather than a standalone answer.
Schöll provides the broadest and most practice-oriented review. Rather than focusing on one assay, the authors compare the rapidly expanding landscape of commercial tests and devote substantial attention to issues that determine whether biomarkers can realistically be adopted in routine care. Their review argues that plasma biomarkers should become part of a standardized diagnostic pathway extending from primary care through specialty memory clinics. Among currently available markers, they conclude that p-tau217 consistently demonstrates the strongest diagnostic performance. At the same time, they emphasize practical issues—including assay automation, laboratory standardization, pre-analytical variability, patient comorbidities, and interpretation of intermediate ("gray zone") results—that must be addressed before widespread implementation. A particularly useful contribution is their catalog of currently available commercial assays and discussion of their differing regulatory status, including research-use-only assays, laboratory-developed tests, and fully regulated in vitro diagnostic devices.
Teunissen takes a somewhat different perspective by concentrating specifically on plasma p-tau immunoassays rather than Alzheimer's biomarkers more generally. The review explains why different phosphorylated tau species reflect different stages of disease biology. P-tau231 appears to rise earliest with initial amyloid accumulation, whereas p-tau217 demonstrates particularly strong relationships to both amyloid pathology and early tau pathology, making it the leading candidate for routine clinical diagnosis. The authors also emphasize that not all p-tau217 assays perform identically; assay design, antibodies, analytical platforms, and calibration materially influence performance. Consequently, they argue that assay standardization and rigorous head-to-head comparisons remain priorities before biomarkers can be fully interchangeable across laboratories.
Areas of agreement
The three reviews display striking consensus.
First, all conclude that plasma p-tau217 currently represents the leading blood biomarker for Alzheimer's disease because of its combination of diagnostic accuracy, association with amyloid pathology, and practical clinical performance.
Second, all view blood biomarkers as complements—not immediate replacements—for PET imaging and cerebrospinal fluid testing. Instead, they envision a sequential diagnostic pathway in which blood testing serves as an inexpensive, widely accessible first-line test, with PET or CSF reserved for indeterminate or high-stakes cases.
Third, all argue that the emergence of disease-modifying anti-amyloid therapies fundamentally changes the importance of accurate biomarker diagnosis. Blood testing is no longer simply about improving diagnosis; it has become essential for identifying appropriate treatment candidates.
Differences in emphasis
The differences among the reviews lie primarily in emphasis rather than disagreement.
Wisch is the most immediately clinical, interpreting what FDA approval means for practicing physicians and emphasizing how blood testing can "rule in" and especially "rule out" Alzheimer's disease in symptomatic patients.
Schöll is the most implementation-oriented, focusing on laboratory performance, commercial platforms, regulatory pathways, and practical deployment across healthcare systems.
Teunissen is the most analytical and biologically focused, carefully distinguishing among p-tau181, p-tau217, p-tau231, and other tau species while examining assay methodology in considerable technical detail.
Overall perspective
Taken together, these reviews suggest that the field has entered a new phase. The central scientific question is no longer whether blood biomarkers can detect Alzheimer's pathology—they clearly can. The remaining questions concern how best to deploy them.
That shift is reflected in current payer policy. Recent commercial coverage policies, such as Anthem's, increasingly treat plasma biomarkers as the preferred first-line test, reserving PET imaging and CSF analysis for confirmatory testing or difficult cases. Likewise, CMS's withdrawal of the National Coverage Determination for amyloid PET reflects a world in which biomarker-confirmed diagnosis has become integral to selecting patients for disease-modifying therapy.
In that sense, the debate has evolved. A decade ago, policymakers asked whether biomarkers had sufficient clinical utility to justify coverage. Today, the question is increasingly which biomarker should be used first, under what circumstances confirmatory testing is required, and how to standardize an expanding marketplace of assays without sacrificing diagnostic accuracy.
References
Wisch JK, Ances BM. Ruling in, ruling out: the clinical utility of plasma biomarkers in diagnosis of Alzheimer's disease. Journal of Clinical Investigation. 2025;135:e198725.
Schöll M, Vrillon A, Ikeuchi T, et al. Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use. Journal of Prevention of Alzheimer's Disease. 2025;12:100056.
Teunissen CE, Kolster R, Triana-Baltzer G, et al. Plasma p-tau immunoassays in clinical research for Alzheimer's disease. Alzheimer's & Dementia. 2025;21:e14397.
