Modifiedmedical mutual - ohioPolicy AHS - G2048 - Biochemical Markers of Alzheimer Disease and Dementia

Biochemical Markers of Alzheimer Disease and Dementia

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Defines coverage policy for biochemical biomarker testing (CSF, plasma, urine, other media) used in evaluation of suspected Alzheimer disease or mild cognitive impairment and specifies which tests meet or do not meet coverage criteria for Medical Mutual - Ohio members.

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Modifiedmedical mutual - ohioPolicy AHS - G2048 - Biochemical Markers of Alzheimer Disease and Dementia

Biochemical Markers of Alzheimer Disease and Dementia

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Policy Summary

Payermedical mutual - ohio

PolicyBiochemical Markers of Alzheimer Disease and Dementia

Policy CodePolicy AHS - G2048 - Biochemical Markers of Alzheimer Disease and Dementia

Change TypeCoverage addition (new covered plasma ratio) and coding updates

Effective DateFeb 1, 2026

Last ReviewSep 4, 2025

Next Review DateSep 4, 2025

Key ActionVerify member benefits and obtain prior authorization when required before ordering covered CSF biomarkers or the FDA‑approved plasma p-tau217/Aβ42 ratio test.

SourceLink

POLICY UPDATE CHANGES

New coverage allowance for measurement of the ratio of p-tau217 to Aβ42 in plasma using an FDA-approved test.

Reorganized former CC2 and CC3 into CC3 and CC4 to align with new allowances for CC1 and CC2.

Measurement of certain biomarkers in plasma/serum as allowed previously was explicitly marked as not meeting coverage criteria (remains not covered for many individual plasma markers).

Multiple new CPT codes were added to the policy coding list (e.g., 0596U, 0568U, 0547U, 0548U, 0551U, 82233, 82234, 83884, 84393, 84394).

1New covered plasma ratio

MultipleCSF measures covered

ManyNon-covered plasma/serum tests

ExamplesProprietary assays cited

MultipleNew CPT codes added

Coverage Criteria for Biochemical Markers

inv-01: Covered tests

Covered when testing is for individuals with suspected Alzheimer disease or mild cognitive impairment and the specific biomarkers below are measured:

CSF biomarkers covered: Measurement of cerebrospinal fluid (CSF) amyloid beta peptides AND/OR the ratio of total tau (t-tau) to Aβ42 AND/OR the ratio of phosphorylated tau 181 (p-tau181) to Aβ42 meets coverage criteria for individuals with suspected Alzheimer disease or mild cognitive impairment.

Text lists these CSF biomarkers as meeting coverage criteria.

Plasma biomarker covered: Measurement of the ratio of p-tau217 to Aβ42 in plasma using an FDA-approved test (example: Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio) meets coverage criteria for individuals with suspected Alzheimer disease or mild cognitive impairment.FDA-approved assay required

Policy explicitly cites plasma p-tau217/Aβ42 FDA-approved test as covered.

inv-02: Not covered / excluded tests

Not covered tests (do not meet coverage criteria):

Other CSF biomarkers not listed: Measurement of CSF biomarkers of Alzheimer disease or dementia not mentioned above (e.g., α-synuclein, neural thread proteins) does not meet coverage criteria.

Policy explicitly excludes these CSF analytes.

Plasma/serum biomarkers other than specified: Measurement of plasma and/or serum biomarkers of Alzheimer disease or dementia (e.g., p-tau217 or Aβ42 as individual markers, total tau protein, amyloid beta 1-40, neural thread proteins, ApoE, ApoE4) does not meet coverage criteria unless the specific FDA-approved plasma p-tau217/Aβ42 ratio test is used.

Policy excludes general plasma/serum biomarker testing; an FDA-approved plasma ratio test is an exception listed elsewhere.

Urine biomarkers: Measurement of urinary biomarkers of Alzheimer disease or dementia (e.g., neural thread proteins, amyloid beta peptides, urinary extracellular vesicle analysis) does not meet coverage criteria.

Policy explicitly excludes urine biomarkers.

Multianalyte/algorithmic tests: Use of multianalyte assays, algorithmic analysis, and/or any other tests not mentioned in the covered list for prognosis, diagnosis, or management of Alzheimer disease or dementia does not meet coverage criteria.

inv-03: Appropriate use contexts

Covered/acceptable contexts per guidelines

Specialist clinic symptomatic patients: Blood-based biomarkers (BBMs) with established thresholds should currently only be used in symptomatic patients at specialist memory clinics, and results should be confirmed with CSF or PET whenever possible.established thresholds

Alzheimer's Association and other guideline sources recommend restricted use in specialist settings with confirmatory testing.

Clinical trials and investigational studies: Use of biomarkers is appropriate in investigational studies and clinical trials; BBMs may be used as pre-screeners for trials but should not be primary endpoints.n/a

Guidance cautions controlled implementation and further research before broad clinical use.

inv-04: Coverage guidance and appropriate indications

Guiding statements from professional organizations on appropriate uses of amyloid and tau biomarkers

Appropriate uses: Amyloid PET is appropriate to determine eligibility for approved amyloid-targeting therapy and to inform prognosis in MCI due to suspected AD pathology; CSF biomarkers are recommended as an add-on to clinical evaluation in MCI to predict conversion to AD dementia and functional decline.

Derived from consensus ratings and guideline statements.

Prioritized testing: CSF investigation is prioritized because it provides simultaneous information on amyloid β and tau and is less expensive than PET; PET is an alternative if lumbar puncture is contraindicated.

IWG recommendation prioritizing CSF over PET for simultaneous biomarker information.

Not recommended uses: Nonmedical uses (e.g., legal, insurance, employment screening) and use in lieu of genotyping for suspected autosomal dominant mutation carriers are considered rarely appropriate and are discouraged.

Consensus ratings from AA/SNMMI.

inv-05: When to consider CSF or PET testing

Guideline-based indications and limitations

NICE guidance for further testing: Consider CSF examination (total tau and/or p-tau181 and amyloid beta 1-42 +/- 1-40) or FDG-PET/perfusion SPECT only if the diagnosis is uncertain and knowing the dementia subtype would change management; do not use APOE genotyping or EEG to diagnose Alzheimer disease; be aware of higher false positives with CSF in older persons.

Based on NICE 2018 recommendations.

inv-06: Screening for cognitive impairment

Screening stance

USPSTF screening recommendation: Current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults.

USPSTF 2020 statement.

inv-07: Guideline consensus for selective testing

Selective use and diagnostic contexts

IWG/EFNS/CCCDTD positions: International and specialty groups recommend CSF biomarkers to differentiate Alzheimer disease in cases of diagnostic uncertainty, for early-onset dementia (<65), or for atypical presentations; routine CSF testing is not recommended for all patients.

Sources include IWG, EFNS, and CCCDTD guidance.

inv-08: Updated coverage and non-coverage criteria

Coverage and non-coverage statements updated; includes a new covered plasma ratio test and explicit non-coverage for many other biomarkers.

CC2 (new): For individuals with suspected Alzheimer disease or mild cognitive impairment, measurement of the ratio of p-tau217 to Aβ42 in plasma using an FDA-approved test (e.g., Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio) MEETS COVERAGE CRITERIA.

Added as a new covered criteria in the revision history.

CC3: Measurement of cerebrospinal fluid biomarkers of Alzheimer disease or dementia not mentioned above (e.g., α-synuclein, neural thread proteins) DOES NOT MEET COVERAGE CRITERIA.

Former CC2/CC3 renumbered to align with new allowances.

CC4: Measurement of plasma and/or serum biomarkers of Alzheimer disease or dementia (e.g., p-tau217 or Aβ42 as individual markers, total tau protein, amyloid beta 1-40, neural thread proteins, ApoE, ApoE4) DOES NOT MEET COVERAGE CRITERIA.

Explicit non-coverage for many individual blood biomarkers remains.

Measurement of cerebrospinal fluid biomarkers that are not explicitly listed in the covered criteria (for example, α-synuclein or neural thread proteins) is not covered. Likewise, measurement of plasma or serum biomarkers is not covered unless the specific FDA-approved plasma p-tau217/Aβ42 ratio test is used. Urinary biomarkers and multianalyte/algorithmic assays are also excluded and therefore at risk for denial.

Guideline groups do not endorse routine use of Alzheimer disease blood-based biomarkers (BBMs) for general diagnostic purposes in primary care. BBMs may be useful in specialized settings or trials, but they should not be used as stand-alone diagnostic measures; results should be interpreted in the clinical context and, when possible, confirmed with CSF or PET testing.

Use of amyloid or tau biomarker testing for nonmedical purposes (such as legal evaluation, insurance underwriting, or employment screening) is explicitly discouraged and considered highly inappropriate; such uses would not meet coverage criteria.

Biomarker testing is not recommended for routine screening of asymptomatic older adults because evidence is insufficient to support screening. The USPSTF found current evidence insufficient to assess benefits versus harms of screening for cognitive impairment in older adults. Per NICE, APOE genotyping and EEG should not be used to diagnose Alzheimer disease.

Measurement of cerebrospinal fluid analytes that are not specifically allowed (for example, α-synuclein or neural thread proteins) does not meet coverage criteria. In addition, many individual plasma or serum markers (for example, p‑tau217 or Aβ42 when measured alone, total tau, Aβ40, ApoE/ApoE4) remain explicitly not covered except for the single FDA-approved plasma p‑tau217/Aβ42 ratio described elsewhere in the policy.

Excluded biomarker tests are labelled as 'DOES NOT MEET COVERAGE CRITERIA' because available published literature does not yet confirm clinical benefit or consistent, standardized performance across settings. The policy therefore denies coverage for those tests pending adequate evidence of clinical utility and reproducible validation.

Consensus guidance rates amyloid and tau imaging as rarely appropriate for cognitively unimpaired individuals without elevated risk, and likewise inappropriate for nonmedical screening uses. Imaging is recommended selectively—for example, to determine eligibility for amyloid-targeting therapy or when it will affect management—but is not supported as routine testing in asymptomatic persons.

Investigation of pathophysiological biomarkers in cognitively unimpaired individuals is not recommended for routine clinical practice. Current guidance limits biomarker evaluation in asymptomatic people to research settings or future scenarios where effective prevention or disease-modifying interventions change clinical decision-making.

The USPSTF concludes that evidence is insufficient to support screening of asymptomatic older adults for cognitive impairment; therefore, routine biomarker screening in this population is not indicated under this policy and would not generally meet medical necessity criteria.

Measurement of individual plasma or serum biomarkers alone (for example, p‑tau217 or Aβ42 measured independently, total tau, Aβ40, neural thread proteins, ApoE/ApoE4) does not meet coverage criteria and remains excluded unless performed as the specified FDA‑approved plasma p‑tau217/Aβ42 ratio assay that the policy explicitly allows.

Procedure Codes and Coding Guidance

Applicable CPT/HCPCS procedure codesmixed

No codes listed

Applicable CPT/HCPCS Procedure Codes (selected)mixed

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)
0206U	Neurology (Alzheimer disease); cell aggregation using morphometric imaging and protein kinase C-epsilon (PKCe) concentration in response to amylospheroid

Proprietary (U-code) tests and additional CPTsmixed

0207U	Proprietary test: DISCERN™ mRNA/gene expression profiling (NeuroDiagnostics)
0289U	Proprietary test: MindX Blood Test™ - Memory/Alzheimer's (MindX Sciences)
0358U	Proprietary test: Lumipulse® G β-Amyloid Ratio (1-42/1-40) Test (Fujirebio)
0393U	Proprietary test: SYNTap® Biomarker Test (Amprion)
0412U	Proprietary test: PrecivityAD® blood test (C2N Diagnostics LLC)
0443U	B-amyloid (abeta42) and phospho tau (181p) (ptau181), ECLIA, CSF ratio (Elecsys)
0479U	Proprietary test: ALZpath pTau217 (Neurocode/Quanterix/ALZpath)
0503U	Proprietary test: PrecivityAD2™ (C2N Diagnostics)
0547U	Proprietary test: Neurofilament Light Blood Test
0548U	Glial fibrillary acidic protein (GFAP), plasma assay

1–10 of 11

1/2

Off-cycle added CPT codesCPT

0596U
0568U
0547U
0548U
0551U
82233
82234
83884
84393
84394

WHO blood-based biomarker performance — minimum sensitivity and specificity target

WHO minimum performance targetMinimum sensitivity and specificity of 90% versus a valid reference standard (e.g., neuropathology, amyloid PET, or approved CSF assays)

Intended use populationIndividuals with cognitive impairment consistent with ICD-11 as established by a trained health‑care professional

Specimen type guidancePeripheral blood (plasma or dried blood spots) preferred over CSF for safety and lower infrastructure needs

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Coverage applies to specified CSF biomarkers

For individuals with suspected Alzheimer disease (AD) or mild cognitive impairment (MCI), verify whether measurement of CSF amyloid beta peptides, the ratio of total tau (t‑tau) to Aβ42, or the ratio of phosphorylated tau 181 (p‑tau181) to Aβ42 is being ordered — these CSF measures meet coverage criteria and should be considered first-line when clinically appropriate.

Verify indication: suspected AD or MCI.
Order CSF assays only for covered analytes: amyloid beta peptides; t‑tau/Aβ42; p‑tau181/Aβ42.

Note

Use PET only when results will change management

Consider amyloid and tau PET only after a comprehensive clinical evaluation when AD is the likely etiology and when results are expected to change management (examples: younger-onset or equivocal CSF results); order imaging when it will affect diagnosis, prognosis, or treatment eligibility.

Use PET when AD is likely after standard evaluation and when findings will alter management or therapy eligibility.

Background and Rationale

Alzheimer disease is a progressive neurodegenerative disorder characterized by memory decline, brain atrophy, and the accumulation of amyloid plaques and tau tangles. Biomarkers in CSF and blood can detect underlying pathophysiology before symptoms appear, but assay performance, standardization, and demonstrated clinical utility vary; accordingly, coverage is limited to specific validated CSF measures and the FDA‑approved plasma p‑tau217/Aβ42 ratio in the contexts described by the policy.

Definitions and Key Terms

Cerebrospinal fluid (CSF) definition

DefinitionCerebrospinal fluid (CSF): clear bodily fluid surrounding the brain and spinal cord; listed in the policy Table of Terminology as 'CSF'

Specimen roleProvides fluid biomarkers (amyloid and tau) used to detect Alzheimer pathology when analyzed as Aβ and tau measures

Regulatory contextCSF assays include FDA-cleared tests (e.g., Elecsys CSF assays) referenced elsewhere in the policy

Phosphorylated tau / total tau definition (p-tau / t-tau)

DefinitionPhosphorylated tau (p‑tau) and total tau (t‑tau): forms of tau protein measured in biofluids; p‑tau denotes phosphorylated species (eg, p-tau181, p-tau217) and t‑tau denotes total tau

Clinical significanceElevated CSF p‑tau or t‑tau combined with decreased Aβ1-42 is part of the AD signature indicating Alzheimer pathology

Policy Revision History

2026-02-01policy_effective_dateLatest

Policy effective date updated.

2025-10-01coding_added

CPT code 0596U added to the policy coding list (effective 2025-10-01).

2025-07-01coding_added

Policy Summary

Payermedical mutual - ohio

PolicyBiochemical Markers of Alzheimer Disease and Dementia

Policy CodePolicy AHS - G2048 - Biochemical Markers of Alzheimer Disease and Dementia

Change TypeCoverage addition (new covered plasma ratio) and coding updates

Effective DateFeb 1, 2026

Last ReviewSep 4, 2025

Next Review DateSep 4, 2025

Key ActionVerify member benefits and obtain prior authorization when required before ordering covered CSF biomarkers or the FDA‑approved plasma p-tau217/Aβ42 ratio test.

SourceLink

On This Page

Policy excludes multianalyte/algorithmic approaches unless specifically listed as covered.

Plasma biomarkers caution: Plasma biomarkers for amyloid and tau pathology are not currently recommended for routine clinical practice and require further standardization and validation before broad clinical use.

IWG position on need for further validation of plasma assays.

Prefer PET for cases with contraindication to lumbar puncture or inconclusive CSF results.

Prior Authorization

Obtain prior authorization when payer coverage applies

Evaluate the added value of any biomarker investigation for the individual patient and obtain prior authorization when required by the payer; availability, cost, and plan coverage may limit use.

Assess whether test results will change management, consider patient age/comorbidity, and document rationale.
Verify plan-specific prior authorization rules before testing.

Billing Rule

Include procedure codes on authorization requests

Reference the policy’s listed CPT and HCPCS (proprietary U) codes when requesting authorization or submitting claims; these codes identify the specific biomarker assays covered or excluded.

Use codes such as 82233, 82234, 83520, 83884, 84393, 84394 and relevant proprietary U‑codes from the policy when requesting prior authorization.
When ordering the FDA‑approved plasma p‑tau217/Aβ42 test, include the corresponding proprietary code (per coding table).

Prior Authorization

Follow existing prior authorization and coding workflows

Coding and prior authorization processes remain unchanged — follow existing lab testing prior authorization workflows; note that multiple new CPT codes were added via off‑cycle modifications and should be included in benefit checks.

Follow standard prior authorization procedures for laboratory testing.
Be aware of new off‑cycle CPT additions (see coding list) when verifying benefits or submitting authorizations.

Note

Not specified

Not specified in this section of the document.

Step Therapy

Limit BBM use to trials and specialist settings

BBMs may be used as screeners for trial recruitment but should not be used as primary trial endpoints; primary care use requires additional data and careful implementation.

Use BBMs for pre‑screening in controlled research settings, not as sole endpoints.
Exercise caution implementing BBMs in primary care — additional validation needed.

Note

Prefer CSF as initial biomarker modality

When feasible, prioritize CSF testing as the initial biomarker approach because it provides simultaneous amyloid and tau information and is less expensive; if lumbar puncture is contraindicated, consider PET as an alternative.

Prefer CSF (amyloid + tau) as first-line biomarker testing.
If LP contraindicated or not possible, order amyloid/tau PET instead.

Note

(Reserved)

Reserved (no short summary provided in source).

Note

(Reserved)

Reserved (no short summary provided in source).

Prior Authorization

Verify member benefits and government policy precedence

Verify the member’s benefits and any prior authorization requirements at the time of the test request; coverage is conditional on the individual’s benefit plan and Medicare/Medicaid rules where applicable.

Confirm member coverage and any payer‑specific prior authorization before testing.
If government (NCD/LCD or state Medicaid) policy conflicts with this policy, the government policy governs determinations.

Documentation Required

Confirm BBM results with CSF or PET when possible

If blood‑based biomarker (BBM) results are used in specialty memory clinic settings, confirm abnormal or unexpected BBM results with CSF or PET whenever possible.

Use confirmatory CSF or PET testing in specialty clinic settings when BBM thresholds are not well established.
Document plans for confirmatory testing when relying on BBMs.

Documentation Required

Document clinical rationale and intended management impact

Document the patient’s clinical phenotype, the clinical rationale for ordering biomarkers, how results will change management, and patient preferences, age, and comorbidities in the medical record.

Record specific phenotype and why biomarker testing is expected to alter care.
Include discussion of alternatives, risks (e.g., LP risks), and implications for trial eligibility or therapy.

Documentation Required

Follow government coverage and LDT validation requirements

If a government coverage policy (NCD/LCD or state Medicaid) conflicts with this policy, that government policy takes precedence; laboratories performing LDTs must validate tests and be CLIA‑certified even if FDA clearance is not required for clinical use.

Follow applicable NCD/LCD or state Medicaid rules when they differ from this policy.
Ensure LDTs are CLIA‑validated and documented per laboratory regulations.

Documentation Required

Document use of FDA‑approved plasma p‑tau217/Aβ42 ratio test

Distinguish the covered FDA‑approved plasma ratio test (p‑tau217/Aβ42) from other plasma/serum biomarker measurements — only the specified FDA‑approved plasma p‑tau217/Aβ42 ratio test meets coverage criteria; other biomarker measurements should be documented per medical necessity if ordered.

If ordering a plasma p‑tau217/Aβ42 ratio test, confirm it uses an FDA‑approved assay (example: Lumipulse G pTau217/ß‑Aβ1‑42).
Measurements of individual plasma or serum biomarkers (e.g., p‑tau217 alone, Aβ42 alone) do not meet coverage criteria.

Denial Risk

Avoid tests that do not meet coverage criteria

Do not order CSF analytes or plasma/serum tests that the policy explicitly lists as not meeting coverage criteria (examples: CSF α‑synuclein, neural thread proteins; plasma p‑tau217 or Aβ42 as single analytes, total tau, Aβ40, ApoE/ApoE4); such tests are at risk for denial.

Avoid ordering excluded CSF biomarkers (α‑synuclein, neural thread proteins) unless clinically justified and documented.
Avoid ordering individual plasma/serum biomarkers that are not the FDA‑approved p‑tau217/Aβ42 ratio.

Denial Risk

Do not use biomarkers for routine diagnostics

Biomarker testing is not recommended for routine diagnostic use in all patients; reserve testing for investigational studies, clinical trials, or when deemed appropriate by clinicians in specialist settings.

Do not use biomarkers routinely for general diagnostic purposes; assess on a case‑by‑case basis.
Limit use to investigational, trial, or specialist clinical contexts per guideline recommendations.

Denial Risk

Nonmedical uses and substitution for genotyping are inappropriate

Do not use biomarkers for nonmedical purposes (e.g., legal, insurance, employment screening) or as a substitute for genotyping in suspected autosomal dominant mutation carriers; such uses are rated highly inappropriate and are likely to be denied.

Exclude nonmedical screening uses and substitute testing for genotyping in hereditary cases.
Document clinical necessity for any biomarker ordered to avoid nonmedical use concerns.

Denial Risk

Ensure clinical usefulness will change management

Order biomarker testing only when results are expected to help diagnose a dementia subtype and when knowing the subtype would change patient management; tests ordered without a clear potential to alter management may be denied.

Ensure testing is likely to change diagnosis, prognosis, or treatment decisions before ordering.
Document how the test result will influence clinical care.

Denial Risk

Denial risk for non‑covered biomarkers

Measurement of CSF biomarkers not listed above (e.g., α‑synuclein, neural thread proteins) and many individual plasma/serum biomarkers (for example p‑tau217 or Aβ42 alone, total tau, Aβ40, neural thread proteins, ApoE/ApoE4) DO NOT MEET COVERAGE CRITERIA and may be denied — avoid ordering these without strong justification and documentation.

Include clinical justification and documentation if an excluded analyte is ordered despite noncoverage risk.
Expect denials for tests explicitly listed as not meeting coverage criteria.

Core analytesp‑tau217, p‑tau181 and p‑tau231 are listed as Core 1 fluid analytes in guideline definitions

Amyloid beta 40 / 42 (Aβ40 / Aβ42) definition

DefinitionAmyloid beta 40 (Aß40) and Amyloid beta 42 (Aß42): peptide species of β-amyloid measured in CSF or plasma; Aß42 is the fluid analyte for A (Aβ proteinopathy)

Clinical roleDecreased CSF/plasma Aß42 (or Aß42/40 ratios) indicates amyloid pathology and is used in combination with tau measures for AD diagnosis

Diagnostic equivalenceCSF Aβ42/40 is considered a Core 1 biomarker and is among tests regarded as diagnostic of AD when abnormal

Core 1 biomarkers — definition and role

DefinitionCore 1 biomarkers: biomarkers that become abnormal around the same time as amyloid PET and whose abnormality can be sufficient to establish a diagnosis of Alzheimer disease

ExamplesCore 1 fluid analytes include Aβ42 (or Aβ42/40), and p‑tau species such as p‑tau181 and p‑tau217

Diagnostic roleAbnormal Core 1 biomarker results (eg, CSF Aβ42/40 or CSF p‑tau/Aβ42) can be diagnostic of AD and inform clinical decision making

Core 2 biomarkers — definition and role

DefinitionCore 2 biomarkers: later-changing biofluid and tau PET biomarkers that provide prognostic information and increase confidence that AD is contributing to symptoms

ExamplesCore 2 fluid analytes include MTBR‑tau243, p‑tau205, nonphosphorylated mid-region tau fragments; imaged by tau PET

Use in practiceCore 2 biomarkers are generally not used as standalone diagnostic tests but add prognostic value

AD signature — decreased CSF Aβ1-42 and increased CSF tau indicating Alzheimer pathology

DefinitionAD signature: combination of decreased CSF Aβ1‑42 together with increased CSF total tau (t‑tau) or phosphorylated tau (p‑tau), indicating Alzheimer pathology

Diagnostic accuracyThe AD signature combination has reported sensitivity of ~90–95% and specificity of ~90% for AD

Interpretation noteCSF biomarkers should be interpreted within the broader clinical context due to inter-laboratory variability and cutoff differences

Blood-based biomarker — definition and recommended performance characteristics

DefinitionBlood-based biomarker (BBM): peripheral blood assays (plasma or dried blood spots) intended to identify AD pathophysiology

Recommended performanceWHO recommends minimum clinical performance of ≥90% sensitivity and specificity versus a valid reference standard for diagnostic use

Current recommendationIWG notes plasma biomarkers are promising but require further standardization and validation before broad clinical adoption

Common analytes — Abeta40, Abeta42, Abeta42/40 ratio, tTau, pTau181/pTau217, NfL, GFAP, etc.

Typical analytesCommon analytes include Aβ40, Aβ42, Aβ42/40 ratio, total tau (tTau), phosphorylated tau (pTau181, pTau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)

Assay typesAssays may be immunoassays, single-molecule array (SiMoA), mass spectrometry, or electrochemiluminescent methods depending on the test

Proprietary examplesProprietary/plasma tests cited in the policy include PrecivityAD, Lumipulse, ALZpath pTau217, LucentAD, and others

Laboratory-developed test (LDT) — definition and regulatory context

DefinitionLaboratory‑developed test (LDT): an in‑house test validated and performed by the laboratory under CLIA; not FDA‑approved but regulated as high‑complexity tests by CMS

Regulatory noteLDTs are not FDA approved or cleared; laboratories must validate LDTs and be CLIA‑certified for clinical use

Policy contextFDA clearance is not required for clinical use of LDTs, but FDA‑cleared commercial assays (eg, Elecsys, Lumipulse plasma ratio) are specifically referenced in the policy

p-tau217/Aβ42 plasma ratio — definition and example (Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio)

Definitionp‑tau217/Aβ42 plasma ratio: a plasma assay measuring the ratio of phosphorylated tau 217 to amyloid beta 1‑42

Example meeting coveragePolicy cites the FDA‑permitted marketing example: Lumipulse G pTau217/ß‑Amyloid 1‑42 Plasma Ratio as an FDA‑permitted/approved test intended to identify patients with amyloid pathology

Intended use noteIntended for patients over age 50 with signs or symptoms of cognitive decline and not intended as a screening or stand‑alone diagnostic tool; results must be combined with clinical information

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

2025-04-01coding_added

Off-cycle coding modification added proprietary CPT codes 0547U, 0548U, and 0551U (effective 2025-04-01).

2025-03-05coding_entry_note

Documentation notes an off-cycle coding modification with dates referencing the 7/1/2025 effective date for certain additions.

2024-12-04coding_added

Off-cycle coding modification added CPT codes 82233, 82234, 83884, 84393, and 84394 (effective 2025-01-01).

2024-12-04coverage_change

Added new coverage criterion CC2: measurement of the plasma p-tau217/Aβ42 ratio using an FDA-approved test (example: Lumipulse G pTau217/ß-Amyloid 1-42) MEETS COVERAGE CRITERIA; prior CC2/CC3 renumbered to CC3/CC4 and edited for consistency.