Modifiedmedical mutual - ohioPolicy AHS - G2048

Biochemical Markers of Alzheimer Disease and Dementia

Defines which biochemical biomarker tests for Alzheimer disease (AD) and dementia are covered or not covered by Medical Mutual - Ohio and specifies indications, limitations, and related proprietary tests; applies to evaluation of individuals with suspected AD or mild cognitive impairment.

Policy Summary

Payermedical mutual - ohio

PolicyBiochemical Markers of Alzheimer Disease and Dementia

Policy CodePolicy AHS - G2048

Change TypeCoverage criteria revisedplasma ratio addedcoding update

Effective DateFeb 1, 2026

Next Review DateSep 4, 2025

Key ActionOrder covered CSF amyloid/tau ratios or the FDA-approved plasma p-tau217/Aβ42 ratio only for individuals with suspected AD or MCI and document clinical indication.

SourceLink

POLICY UPDATE CHANGES

CC1 edited to allow p-tau/Aβ42 and t-tau/Aβ42 ratio in CSF.

New CC2 allows measurement of the p-tau217/Aβ42 ratio in plasma using an FDA-approved test (example: Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio).

Former CC2 and CC3 were renumbered (now CC3 and CC4) and edited for consistency with new CC1 and CC2 allowances.

Off-cycle coding modification added CPT code 0568U (effective 7/1/2025).

coveredCSF biomarkers

coveredPlasma p-tau217 ratio (FDA)

not covered

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Other plasma/serum/urine

~30+Procedure codes listed

Coverage Criteria for Biochemical Biomarkers

Covered biomarkers for suspected AD/MCI

Covered when ALL of the following are met:

ALL of the following

Individual presents with suspected Alzheimer disease or mild cognitive impairment (MCI).
Testing is performed on cerebrospinal fluid (CSF) and the analyte is one of the following: amyloid beta peptides; the ratio of total tau (t-tau) to amyloid beta 1-42 (Aβ42); or the ratio of phosphorylated tau 181 (p-tau181) to Aβ42.
For plasma testing, the ratio of p-tau217 to Aβ42 is measured using an FDA-authorized/approved test (e.g., Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio).
Test results are interpreted in the context of the full clinical evaluation; results are not used alone to establish the diagnosis (except as specified by FDA intended use and lab/assay labeling).

Not medically necessary / Not covered biomarkers

Not covered when ANY of the following specimen types, analytes, or test classes are requested:

ANY of the following

Measurement of CSF biomarkers of Alzheimer disease or dementia not listed in the covered criteria (for example, α-synuclein, neural thread proteins).
Measurement of plasma and/or serum biomarkers when reported as individual markers that are not part of an FDA-authorized intended use (for example, p-tau217 or Aβ42 alone, total tau protein, amyloid beta 1-40, neural thread proteins, ApoE, ApoE4).
Measurement of urinary biomarkers of Alzheimer disease or dementia (for example, neural thread proteins, amyloid beta peptides, urinary extracellular vesicle analysis).
Multianalyte assays, algorithmic analyses, or other proprietary combinatorial tests not specified in the covered criteria (including multianalyte panels or algorithm-derived risk scores) when used for prognosis, diagnosis, or management of AD/dementia.

FDA-intended use limitations

FDA-intended use limitations (operational constraints to align coverage with authorized indications):

ALL of the following

Coverage for FDA-authorized or cleared biomarker assays is limited to the test's labeled intended use population and indications; tests must be administered and interpreted per the manufacturer's instructions and intended use statements.
The Fujirebio Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio test is covered only for patients over age 50 who present with signs or symptoms of cognitive decline and when the test is used as an adjunct to clinical assessment (it is not covered as a screening tool or a standalone diagnostic).
FDA-cleared/authorized CSF assays (e.g., Roche Elecsys CSF Abeta42/Abeta42 ratios and pTau181/tTau assays) are covered only in the populations and age ranges specified in their clearances and where testing will inform clinical management in symptomatic individuals.
Results from FDA-authorized tests must be integrated with clinical findings; coverage does not extend to use of these assays outside their intended-use claims (for example, in asymptomatic screening, for unrelated indications, or in populations not specified by the FDA authorization).

Procedure Codes and Coding Guidance

Listed CPT/HCPCS codesCPT

82233	Beta-amyloid; 1-40 (Abeta 40)
82234	Beta-amyloid; 1-42 (Abeta 42)
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified
83884	Neurofilament light chain (NfL)
84393	Tau, phosphorylated (eg, pTau 181, pTau 217), each
84394	Tau, total (tTau)

Listed HCPCS U-codes and proprietary testsHCPCS

0206U	Neurology (Alzheimer disease); cell aggregation using morphometric imaging and protein kinase C-epsilon (PKCe) concentration in response to amylospheroid — Proprietary test: DISCERN™
0207U	Quantitative imaging of phosphorylated ERK1 and ERK2 in cultured skin fibroblasts — Proprietary test: DISCERN™
0289U	Neurology (Alzheimer disease), mRNA gene expression profiling by RNA sequencing of 24 genes — Proprietary test: MindX Blood Test™
0358U	Analysis of β-amyloid 1-42 and 1-40, chemiluminescence enzyme immunoassay, CSF — Proprietary test: Lumipulse® G β-Amyloid Ratio (1-42/1-40)
0393U	Fujirebio Diagnostics, Inc. proprietary test (listed)
0412U	Beta amyloid, Aβ42/40 ratio, LC-MS/MS and ApoE proteotyping, plasma combined with age — Proprietary test: PrecivityAD®
0443U	Neurofilament light chain (NfL), ultra-sensitive immunoassay, serum or CSF — Proprietary test: Neurofilament Light Chain (NfL)
0445U	B-amyloid (abeta42) and phospho tau (181p) (ptau181), ECLIA, CSF, ratio reported — Proprietary test: Elecsys® PhosphoTau (181P) CSF and βAmyloid (1-42) CSF II Ratio
0459U	β-amyloid (Abeta42) and total tau (tTau), ECLIA, CSF, ratio reported — Proprietary test: Elecsys® Total Tau CSF and βAmyloid (1-42) CSF II Ratio
0479U	Tau, phosphorylated, pTau217 — Proprietary test: ALZpath pTau217

1–10 of 16

1/2

Policy-recognized CPT codes (added/updated)CPT

0568U	Added CPT code (off-cycle coding modification, effective 7/1/2025)
0547U	Previously added CPT code (off-cycle modification)
0548U	Previously added CPT code (off-cycle modification)
0551U	Previously added CPT code (off-cycle modification)
82233	Added CPT code (effective 01/01/2025)
82234	Added CPT code (effective 01/01/2025)
83884	Added CPT code (effective 01/01/2025)
84393	Added CPT code (effective 01/01/2025)
84394	Added CPT code (effective 01/01/2025)

Removed CPT codesCPT

0346U

Removed CPT code (effective 01/01/2025)

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Amyloid/Tau PET appropriateness

Amyloid and tau PET imaging should be ordered only when consistent with updated Appropriate Use Criteria (Alzheimer's Association / SNMMI 2025). Use is appropriate when: a dementia expert has evaluated the patient and AD is a likely etiology but remains uncertain after comprehensive evaluation; knowledge of amyloid/tau status is expected to change management; and the specific clinical scenario scores in the 'appropriate' range per the A/T PET criteria (examples include MCI or dementia <65 with suspected AD, atypical presentations, or determining eligibility for approved amyloid-targeting therapy). Document clinical scenario and rationale in the medical record.

Appropriate Use Criteria (2025 Alzheimer's Association / SNMMI) should guide ordering decisions.
Document how PET results are expected to change management (diagnosis, prognosis, treatment eligibility).

Documentation Required

Coverage contingent on approval/reimbursement

Coverage and clinical use of biomarker tests — particularly PET imaging — is conditional on regulatory marketing authorization and payer reimbursement. If an imaging modality or specific assay does not have local regulatory approval or is not reimbursed by the payer, coverage is not implied and prior authorization may be denied.

Background and Evidence Summary

Alzheimer disease is a progressive neurodegenerative disorder characterized by decline in memory and cognition and by accumulation of amyloid plaques and neurofibrillary tangles. Biochemical biomarkers can reflect these pathophysiological processes: cerebrospinal fluid measures of amyloid beta and tau (including t‑tau/Aβ42 and p‑tau181/Aβ42 ratios) and certain FDA‑approved plasma assays (for example, the p‑tau217/Aβ42 plasma ratio) are recognized in this policy as informative in individuals with suspected AD or mild cognitive impairment when used in appropriate clinical contexts. However, many proposed biomarkers lack standardization and established clinical utility outside specialist settings, which underlies the policy's selective coverage approach.

Definitions and Key Terms

inv-45: CSF — Cerebrospinal fluid

DefinitionCerebrospinal fluid (CSF)

Specimen contextCSF is the fluid sampled by lumbar puncture used to measure amyloid and tau biomarkers for suspected AD/MCI

Role in policyCSF biomarker measurements (Aβ peptides, t-tau/Aβ42 and p-tau181/Aβ42 ratios) are specified as meeting coverage criteria

inv-46: p-tau / t-tau — Phosphorylated tau / total tau proteins measured as AD biomarkers

Definitionp-tau / t-tau = phosphorylated tau and total tau proteins measured as Alzheimer disease biomarkers

Common assaysp-tau181 and p-tau217 cited as specific phosphorylated tau isoforms used in CSF and plasma assays

Revision History and Policy Updates

2026-02-01policy_effective_dateLatest

Policy effective date after review incorporating coverage changes allowing CSF t-tau/Aβ42 and p-tau181/Aβ42 ratios and permitting plasma p-tau217/Aβ42 ratio using an FDA-approved assay.

2025-09-04coverage_criteria_revision

Revised coverage criteria: CC1 edited to explicitly allow CSF p-tau/Aβ42 and t-tau/Aβ42 ratios; CC2 added to permit measurement of plasma p-tau217/Aβ42 ratio when performed with an FDA-approved test; former CC2/CC3 renumbered and edited for consistency.

2025-06-04

Policy Summary

Payermedical mutual - ohio

PolicyBiochemical Markers of Alzheimer Disease and Dementia

Policy CodePolicy AHS - G2048

Change TypeCoverage criteria revisedplasma ratio addedcoding update

Effective DateFeb 1, 2026

Next Review DateSep 4, 2025

Key ActionOrder covered CSF amyloid/tau ratios or the FDA-approved plasma p-tau217/Aβ42 ratio only for individuals with suspected AD or MCI and document clinical indication.

SourceLink

On This Page

Use of biomarkers or testing in individuals without established cognitive impairment (screening of asymptomatic individuals) or for nonmedical purposes (e.g., employment, insurance, legal matters).

Laboratory-developed tests (LDTs) or tests without FDA authorization/clearance remain noncovered or investigational for indications beyond those explicitly recognized by this policy unless regulatory status and clinical evidence change.

IWG recommends amyloid/tau PET in practice only when regulatory approval and reimbursement are in place.
Verify FDA/CMS/Local Coverage status before ordering; consult payer prior authorization rules.

Billing Rule

Procedure codes potentially subject to prior authorization

The following CPT/HCPCS and proprietary U-codes listed in the policy may be subject to payer prior authorization and other coverage controls. Ordering providers should confirm prior authorization requirements with Medical Mutual - Ohio before scheduling or billing.

Common laboratory CPT codes: 82233, 82234, 83520, 83884, 84393, 84394.
Proprietary / U-codes included in this policy: 0206U, 0207U, 0289U, 0358U, 0393U, 0412U, 0443U, 0445U, 0459U, 0479U, 0503U, 0547U, 0548U, 0551U, 0568U, 0596U.

Billing Rule

Procedure code updates (example)

Newly added or updated procedure codes in this policy (example): CPT code 0568U was added effective 7/1/2025. Providers and billing staff must follow payer-specific prior authorization and billing rules for any recently added codes.

0568U added 07/01/2025 (policy revision noted 06/04/2025).
Follow Medical Mutual prior authorization rules for new codes.

Denial Risk

Denial triggers for non-covered biomarker tests

Tests not listed as meeting coverage criteria may be denied. Common denial triggers include requests for: individual plasma or serum markers outside the specifically allowed FDA-approved plasma ptau217/Aβ42 ratio test, urinary biomarkers, unspecified CSF biomarkers not enumerated in coverage criteria, and multianalyte proprietary algorithms that are not covered.

Plasma/serum biomarkers (e.g., individual p-tau217, Aβ42 alone) are NOT covered except the FDA-authorized plasma p-tau217/Aβ42 ratio test.
Unlisted CSF biomarkers (e.g., α-synuclein, neural thread proteins) DO NOT meet coverage criteria.
Multianalyte algorithms not specified as covered may be denied.

Note

Routine use discouraged by NIA-AA (2011)

Per the 2011 NIA-AA workgroup, routine use of AD biomarker testing for diagnostic purposes is not recommended outside of specific circumstances (investigational studies, clinical trials, or specialist settings). Clinicians should not order biomarker tests routinely for all patients.

NIA-AA (2011) advises against routine diagnostic use of biomarkers due to standardization, availability, and evidence limitations.
Reserve biomarker testing for cases where results will affect management or for specialist/ research settings.

Documentation Required

Target population restrictions

Target population restrictions: biomarker testing is intended for individuals with suspected Alzheimer disease or mild cognitive impairment (progressive cognitive decline evaluated by a trained clinician). Do not offer these tests to individuals without established cognitive impairment, to persons currently receiving disease-modifying therapies, or to participants in disease-modifying clinical trials unless specifically indicated and covered.

WHO target population: symptomatic individuals with established cognitive impairment; excludes unimpaired individuals and those on disease-modifying therapies or in related clinical trials.
Document cognitive status and why testing is indicated.

Documentation Required

Conflicting government policy

If there is a conflict between this policy and applicable government policies (e.g., LCDs, NCDs, or state Medicaid rules), the government policy governs adjudication of coverage. Verify local Medicare/Medicaid coverage rules when ordering.

Government policies (NCDs/LCDs) take precedence over plan policy when applicable.
Check CMS and state Medicaid sites for current coverage guidance prior to ordering.

Documentation Required

Clinical indication documentation

Clinical indication documentation: when ordering covered CSF biomarker tests or the specified FDA-authorized plasma p-tau217/Aβ42 ratio test, document in the medical record that the patient has suspected Alzheimer disease or mild cognitive impairment, include relevant history and findings, and state how the test result will affect management.

Record clinical diagnosis (suspected AD or MCI), cognitive testing results, and why biomarker information is needed.
Include documentation of shared decision-making when results could impact major management decisions (e.g., treatment eligibility).

Documentation Required

Clinical justification and test selection

Clinical justification and test selection: clinicians should evaluate the added value of biomarker testing for each symptomatic patient considering age, comorbidity, phenotype complexity, patient preferences, availability, cost, and how results will alter management. Prefer assays and modalities with demonstrated validity and local reimbursement.

Prioritize CSF assays that provide both amyloid and tau information when appropriate.
Document why a particular assay or modality was selected over alternatives (e.g., CSF vs PET).

Documentation Required

Clinical correlation required

Clinical correlation required: All biomarker results must be interpreted in the context of the full clinical evaluation. Some FDA-authorized assays are intended for specific age groups (e.g., plasma Lumipulse pTau217/Aβ42 for patients over 50) and results are not intended as stand-alone diagnoses.

Correlate biomarker findings with clinical assessment, imaging, and cognitive testing.
Note assay-specific intended use and age restrictions in the record when applicable.

Documentation Required

Required clinical indication and assay authorization

Required clinical indication and assay authorization: document that testing is for individuals with suspected AD or MCI and that the specific assay used has appropriate regulatory authorization for the intended use (e.g., FDA marketing authorization or clearance). Unsupported assays may be denied.

For covered plasma testing, document use of an FDA-authorized plasma p-tau217/Aβ42 ratio assay when applicable (e.g., Lumipulse G pTau217/ß-Amyloid 1-42).
For CSF tests, document the specific assay and its authorization status (e.g., Roche Elecsys CSF assays).

Prior Authorization

Biomarker confirmation prior to amyloid-targeting therapy

Biomarker confirmation prior to amyloid-targeting therapy: before initiating an approved amyloid-targeting therapy (for example, lecanemab), confirm elevated brain beta-amyloid using an accepted method (examples include amyloid PET or CSF assays). Document the confirming test result in the chart prior to therapy authorization.

Confirmatory tests acceptable include CSF assays demonstrating amyloid/tau signature or amyloid PET showing tracer retention.
Documentation of confirmation is required before treatment authorization for amyloid-targeting therapies.

Documentation Required

Confirmation before diagnostic use

Confirmation before diagnostic use: blood-based biomarkers (BBMs) should not be used as standalone diagnostic markers outside specialist memory clinic settings. When BBMs are used in specialist clinics, confirmatory CSF or PET testing is recommended whenever possible before making definitive diagnostic or major management decisions.

Use BBMs only in symptomatic patients evaluated in specialist clinics and seek confirmatory CSF or PET when possible.
Avoid using BBM results alone to make major treatment decisions without confirmatory testing.

Note

Preferred testing sequence

Preferred testing sequence: when both CSF and PET could provide needed information, CSF investigation is prioritized because it can provide simultaneous amyloid and tau data and is generally less expensive. If lumbar puncture is contraindicated or not feasible, PET (amyloid and/or tau) is an acceptable alternative.

Prefer CSF first for simultaneous amyloid and tau information when not contraindicated.
If LP contraindicated, proceed to PET imaging as the next-step diagnostic modality.

Policy relevanceCSF p-tau181/Aβ42 and CSF t-tau/Aβ42 ratios meet coverage criteria; p-tau217 referenced for plasma ratio testing

inv-47: Core 1 biomarkers — Biomarkers that become abnormal around same time as amyloid PET; include Aβ42 and phosphorylated tau forms

DefinitionCore 1 biomarkers become abnormal around the same time as amyloid PET

ExamplesFluid analyte Aβ42 and phosphorylated tau forms (p-tau217, p-tau181, p-tau231)

Diagnostic roleAbnormality on specific Core 1 biomarkers can be sufficient to diagnose AD when assays are accurate

inv-48: Core 2 biomarkers — Later-changing biomarkers (fluid and tau PET) that provide prognostic information

DefinitionCore 2 biomarkers are later-changing biomarkers that provide prognostic information

ExamplesFluid analytes: MTBR-tau243, other phosphorylated tau forms (eg, p-tau205), nonphosphorylated mid-region tau fragments; imaged by tau PET

Clinical useCore 2 biomarkers are mainly used for prognosis and are not typically standalone diagnostic tests

inv-49: AD biochemical signature (CSF) — Decreased Aβ1-42 with increased total tau or phosphorylated tau in CSF; combination increases diagnostic accuracy

DefinitionAD biochemical signature (CSF): decreased Aβ1-42 together with increased total tau (T-tau) or phosphorylated tau (P-tau)

Diagnostic performanceCombination of low Aβ1-42 and high T-tau or P-tau increases diagnostic accuracy (reported sensitivity 90–95% and specificity ≈90%)

InterpretationCSF biomarker results should be interpreted in clinical context and are affected by inter-laboratory variability

inv-50: Biomarker positivity per IWG — Amyloid-positive and tau-positive status combined with compatible clinical phenotype required for AD diagnosis per IWG

IWG definitionDiagnosis of AD requires a compatible clinical phenotype plus biomarker evidence of amyloid-positive and tau-positive status

Biomarker combination requirementBoth amyloid and tau biomarker positivity (by CSF or PET) are required to establish Alzheimer disease diagnosis per IWG

Clinical caveatIsolated amyloid positivity in an amnestic phenotype is not specific for AD; clinician judgment is required for uncommon phenotypes

inv-51: CSF biomarker panels — Assays measuring CSF Aβ1-42, Aβ1-40, total tau, and phosphorylated tau used to support AD pathophysiology

Panel componentsCSF biomarker panels measure Aβ1-42, Aβ1-40, total tau (t-tau), and phosphorylated tau (eg, p-tau181)

Clinical utilityCSF panels provide simultaneous amyloid and tau information and are prioritized when lumbar puncture is feasible

Regulatory contextSeveral CSF assays (eg, Lumipulse, Elecsys) have received FDA clearance/marketing authorization for use in defined adult populations

inv-52: Plasma biomarker tests — Blood-based assays measuring Aβ42/40 ratio, pTau isoforms, NfL, GFAP and algorithm scores

Test typesPlasma (blood-based) biomarker tests measure combinations such as Aβ42/40 ratio, pTau isoforms (pTau181, pTau217), NfL, GFAP, and algorithm-derived scores

Intended use limitsPlasma BBMs are promising but require further standardization and validation; some plasma assays have FDA marketing authorization with specific intended uses

Clinical rolePlasma tests may estimate likelihood of brain amyloid pathology but are not universally recommended for routine clinical practice

inv-53: p-tau217/Aβ42 ratio (plasma) — Plasma biomarker ratio measured by an FDA-approved test (example: Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio)

DefinitionPlasma p-tau217/Aβ42 ratio: ratio of phosphorylated tau 217 to amyloid beta 1-42 measured in plasma

Covered exampleMeasurement of the plasma p-tau217/Aβ42 ratio using an FDA-approved test (eg, Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio) meets coverage criteria for suspected AD/MCI

LimitationsFDA-authorized plasma tests are intended for symptomatic adults (eg, >50 years) and not as stand-alone screening tools; results must be integrated with clinical information

inv-54: CSF t-tau/Aβ42 and p-tau181/Aβ42 ratios — CSF ratios described in the policy as meeting coverage criteria

Covered ratiosCSF t-tau/Aβ42 and CSF p-tau181/Aβ42 ratios are explicitly allowed and meet coverage criteria for individuals with suspected AD or MCI

Diagnostic equivalenceCSF p-tau181/Aβ42 and t-tau/Aβ42 are among Core 1 measures regarded as diagnostic of AD when assays are accurate

Policy changeRevision to CC1 in 09/04/2025 operationalized inclusion of CSF p-tau/Aβ42 and t-tau/Aβ42 ratios in coverage criteria

Off-cycle coding modification: added CPT code 0568U (effective 2025-07-01).

2025-03-05coding_update

Off-cycle coding modification: added CPT codes 0547U, 0548U, and 0551U (effective date noted in policy).