Blue Cross Blue Shield RI CSF Biomarker Coverage & Prior Auth

Coverage Criteria

Medically necessary CSF biomarker testing for initiation of amyloid-targeting therapy

Covered when ALL of the following are met

Population: Individual with mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease

Purpose of testing: CSF biomarker testing (amyloid beta and tau proteins) is used as part of an evaluation for the initiation of an approved amyloid beta–targeting therapy

Medicare Advantage and Commercial Products

Exclusions to this indication: Not used as an adjunct to routine clinical diagnosis and not used as part of an evaluation for continuation of amyloid beta–targeting therapy

CSF testing covered specifically for initiation evaluation only

Not covered when evidence insufficient

Evidence insufficient for coverage when any of the following apply

Adjunct to clinical diagnosis: CSF or other biomarker testing used as an adjunct to clinical diagnosis (not specifically for establishing eligibility for initial anti-amyloid therapy)

Not covered / evidence insufficient

Continuation evaluation: CSF or blood biomarker testing used as part of an evaluation for continuation of amyloid beta–targeting therapy

Evidence insufficient to determine effect on health outcomes

Urine or blood biomarkers as adjunct: Measurement of urinary or blood biomarkers used as an adjunct to clinical diagnosis of AD

Clinical validity and net health outcome improvement uncertain; evidence insufficient

Use of CSF biomarkers to establish eligibility for initial anti-amyloid therapy

Covered when ALL of the following are met

Population: Individuals with MCI or mild dementia due to Alzheimer disease who are being considered for initial treatment with an FDA‑approved amyloid beta–targeting therapy

Diagnostic role: CSF biomarkers may be used as an alternative to amyloid PET to establish presence of amyloid beta pathology to determine eligibility for initial anti-amyloid therapy

Evidence sufficient to determine improvement in net health outcome for this use

Test types: CSF core biomarkers (eg, Aβ42, Aβ42/40 ratio, phosphorylated tau, total tau) or specified CSF assays with validated interpretation consistent with trial eligibility

Refer to coding section for covered CPTs and specific test assays

This policy takes a differentiated stance by test and clinical use. CSF-based amyloid and tau biomarker testing (CPT codes 82233, 82234, 84393, 84394, 0358U, 0445U, 0459U) may be considered medically necessary when used to establish amyloid pathology as part of the evaluation for initiation of an approved amyloid‑targeting therapy in individuals with mild cognitive impairment or mild dementia due to Alzheimer disease. Conversely, measurement of Neurofilament Light Chain (NfL) tests (CPT 0361U, 0443U) and the PrecivityAD® plasma test (CPT 0412U) are explicitly listed as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products in the contexts described in this policy.

Prior authorization is required for Medicare Advantage Plans for the CSF biomarker CPTs listed and is recommended for Commercial Products; providers should verify member‑specific prior authorization requirements and follow the ordering/authorization procedures described in this policy.

Benefit determinations are based on the member's subscriber agreement, member certificate, and/or employer agreement, which prevail over this policy. This document is informational and is not a guarantee of payment; providers must verify member‑specific benefits and eligibility with the payer or provider call center prior to ordering tests.

Measurement of urinary and blood biomarkers when used as an adjunct to clinical diagnosis for individuals with mild cognitive impairment or mild dementia due to Alzheimer disease is considered not covered for Medicare Advantage Plans and not medically necessary for Commercial Products. The policy specifically identifies the PrecivityAD® blood test (CPT 0412U) and Neurofilament Light Chain tests (CPT 0361U, 0443U) in this not medically necessary category.

If a service is determined to be not medically necessary or otherwise a non‑covered benefit, the member generally may not be billed for that service unless the member has been informed and has provided a written agreement in advance to self‑pay. Providers should follow the payer's procedures and their provider participation agreement for any advance written agreement to bill a member.

Covered Indications

Evaluation for initiation of amyloid beta targeting therapy in individuals with MCI or mild dementia

CSF biomarker tests considered medically necessary when criteria met

Indication: Evaluation for initiation of amyloid beta–targeting therapy in individuals with MCI or mild dementia due to Alzheimer disease

CSF biomarker testing used to establish amyloid pathology prior to initiating therapy

Covered tests: CPT codes 82233, 82234, 84393, 84394 and specific CSF assay CPTs (0358U, 0445U, 0459U) when submitted in accordance with the medical criteria

See coding section for test descriptions and billing guidance

Laboratory standards: Testing performed by laboratories meeting applicable certification requirements (eg, CLIA high‑complexity for LDTs)

Coding (CPT / HCPCS / ICD-10)

Covered / medically necessary when criteria metmixedCovered

0358U	Lumipulse G ß-Amyloid Ratio (1-42/1-40) (Fujirebio Diagnostics, Inc)
0445U	Elecsys PhosphoTau (181P) CSF (pTau181) and β-Amyloid (1-42) CSF II (Abeta 42) Ratio (Roche Diagnostics)
0459U	Elecsys Total Tau CSF (tTau) and Β-Amyloid (1-42) CSF II (Abeta 42) Ratio (Roche Diagnostics Operations, Inc)
82233	Beta-amyloid; 1-40 (Abeta 40) (New Code Effective 1/1/2025)
82234	Beta-amyloid; 1-42 (Abeta 42) (New Code Effective 1/1/2025)
84393	Tau, phosphorylated (eg, pTau 181, pTau 217), each (New Code Effective 1/1/2025)
84394	Tau, total (tTau) (New Code Effective 1/1/2025)

Not covered / not medically necessaryCPTNot Covered

0361U	Neurofilament light chain, digital immunoassay, plasma (Mayo Clinic)
0443U	Neurofilament light chain (NfL), ultra-sensitive immunoassay, serum or cerebrospinal fluid (Washington University)

Not covered / not medically necessaryCPTNot Covered

0412U

PrecivityAD blood test (Aβ42/40 ratio with ApoE proteotyping and algorithm) (C2N Diagnostics)

Unlisted / may be used; not covered in certain contextsCPT

81099	Unlisted Urinalysis Procedure (used to test urine biomarkers)
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified
86849	Unlisted Immunology Procedure (used to test CSF)

ICD-10 Diagnosis Codes referencedICD-10

F03.90	Unspecified dementia, unspecified
F03.91	Unspecified dementia, with behavioral disturbance
G30.0	Alzheimer disease with early onset
G30.9	Alzheimer disease, unspecified
G31.1	Senile degeneration of brain
G31.84	Mild cognitive impairment, so stated
R41.81	Age-related cognitive decline

Laboratory certification requirement — CLIA high-complexity certification required for LDTs

RequirementLaboratory-developed tests (LDTs) must be performed in a laboratory certified by CLIA for high-complexity testing.

Standards referencedCLIA high-complexity certification is the regulatory standard for LDTs; CAP is also listed as a lab certification in the brief.

FDA contextFDA has not required premarket review of LDTs to date; several AD biomarker tests are available as LDTs.

Practical implicationLabs offering in‑house AD biomarker assays should maintain CLIA high‑complexity certification to meet policy requirements.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage Plans and is recommended for Commercial Products. Providers must verify member-specific benefits and prior authorization requirements with BCBSRI before ordering cerebrospinal fluid (CSF) biomarker testing.

Affected CPT codes/tests: 82233, 82234, 84393, 84394, 0358U, 0445U, 0459U

Note

Check Prior Authorization with Payer

Providers must check and confirm prior authorization and eligibility for each member through the payer’s provider call center or authorization portal prior to performing testing.

Ordering Requirements

Step Therapy

Ordering restrictions — only the ordering physician may handle authorization/appeals

Only the ordering physician may be involved in authorization, appeals, or other administrative processes related to prior authorization/medical necessity; laboratories and their representatives must not act on behalf of the ordering physician.

Ensure the ordering physician conducts and documents any authorization or appeal activities.

Note

Follow member-specific rules and payer–provider agreements for ordering authority

The policy excerpt does not specify who may order tests; follow member-specific benefit rules and applicable payer–provider participation agreements when determining ordering authority.

Adhere to the member's subscriber agreement and your participation agreement for ordering authority details.

Not Covered Services

The following items are explicitly identified as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products: PrecivityAD® (CPT 0412U); Neurofilament Light Chain tests (CPT 0361U, 0443U); and measurement of urinary and blood biomarkers when used as an adjunct to clinical diagnosis in individuals with mild cognitive impairment or mild dementia due to Alzheimer disease.

This excerpt does not provide an exhaustive list of tests or indications that are not covered beyond those explicitly named. Providers should consult member‑specific benefit documents and the payer for any additional non‑covered items or contract‑specific exclusions.

Clinical Background

Alzheimer disease is a progressive neurodegenerative disorder characterized by amyloid plaques and neurofibrillary tangles. Biomarkers reflecting these pathophysiologic processes — including CSF amyloid beta (eg, Aβ42, Aβ42/40 ratio), total tau and phosphorylated tau, and emerging plasma measures such as phosphorylated tau species — are under active investigation and are used clinically to improve diagnostic certainty. CSF biomarkers have comparable diagnostic accuracy to amyloid PET and may be used to establish amyloid pathology when determining eligibility for initial treatment with approved amyloid‑targeting therapies.

Definitions and Biomarker Glossary

Aβ42 definition — Amyloid beta-42 (Aβ42)

AnalyteAmyloid beta-42 (Aβ42) is an amyloid beta peptide produced from amyloid precursor protein and is the key peptide deposited in amyloid plaques characteristic of Alzheimer disease.

CSF patternLow levels of Aβ42 in CSF have been associated with Alzheimer disease, possibly because Aβ42 is deposited in plaques instead of remaining in the CSF.

Clinical useAβ42 measurement (and ratios such as Aβ42/40) is used as a CSF biomarker to help establish amyloid pathology when evaluating for AD and for eligibility for amyloid-targeting therapy.

pTau / tTau definition — phosphorylated tau and total tau clinical significance

AnalytesPhosphorylated tau (eg, pTau181) and total tau (tTau) are CSF proteins associated with neurofibrillary tangles and neurodegeneration.

Frequency Limits

Frequency limits placeholder (no explicit limits in inventory item)

Policy textNo explicit frequency limits are specified in the policy excerpt for CSF or related biomarker testing.

ImplicationProviders should verify member‑specific benefit rules and prior authorization requirements; absence of stated limits does not imply unlimited coverage.

SourcePolicy effective date and administrative notice indicate providers must check benefit documents for applicability.

Frequency limits placeholder (no explicit limits in excerpt)

Document scopeThe policy excerpt does not define numerical frequency limits for biomarker testing; administrative sections advise verification of member benefits.

Provider action

Revision History & References

References and regulatory documents supporting the clinical background and evolving role of biomarkers in Alzheimer's disease care are cited in the policy. Key citations include foundational frameworks and diagnostic guidance (eg, NIA‑AA research framework), methodological and clinical studies of plasma and CSF biomarkers, and regulatory reviews related to anti‑amyloid therapies. This policy and its citations are provided for informational purposes; the policy may be updated as medical evidence and practice evolve.

OpenPayer

Evaluation of Biomarkers for Alzheimer’s Disease — CSF and related biomarker testing