Measurement of CSF, plasma/serum, or urinary biomarkers — Coverage status

Measurement of cerebrospinal fluid (CSF), plasma/serum, or urinary biomarkers for Alzheimer disease or dementia does not meet coverage criteria due to insufficient evidence of clinical benefit. Requests for such testing should include clinical justification and documentation supporting the relevant clinical phenotype and rationale (e.g., to resolve diagnostic uncertainty or inform management). Coverage determinations depend on the individual's benefit plan and applicable Medicare/Medicaid specifications; proprietary assays may have separate coverage rules.

• CSF biomarkers (e.g., tau, phosphorylated tau, Aβ42, Aβ40, Aβ42/Aβ40 ratio, α-synuclein) — NOT COVERED (does not meet coverage criteria).
• Plasma/serum biomarkers (e.g., p-tau181, Aβ42/40, neurofilament light, ApoE) — NOT COVERED (does not meet coverage criteria).
• Urinary biomarkers (e.g., neural thread proteins, urinary extracellular vesicle analysis) — NOT COVERED (does not meet coverage criteria).
• Multianalyte/algorithmic assays and other novel tests for prognosis, diagnosis, or management of AD/dementia — NOT COVERED (does not meet coverage criteria).
• Include clinical justification and documentation of the clinical phenotype when ordering (see documentation callout).

Prior Authorization for CSF Biomarker Testing

Prior authorization may be required for CSF biomarker testing or for specific proprietary assays depending on the member's benefit plan and payer rules. When prior authorization is used, it should be limited to select clinical indications (for example, persistent/progressive MCI, symptoms suggesting alternative etiologies, early-onset presentations, or when results would change management).

• Follow the member's benefit plan for prior authorization requirements; verify coverage before ordering.
• Use CSF testing as an add-on to clinical evaluation or in comparison with imaging biomarkers after stepwise evaluation (consider less invasive testing and clinical assessment first).
• Alzheimer's Association and expert guidance recommend CSF testing in specific indications (see guideline citations).

Billing Code Reference for Proprietary Biomarker Assays

Procedure codes for proprietary biomarker assays are provided in the policy for reference only. Providers should bill under the performing laboratory's NPI and the test-specific code. Procedure codes listed in Medical Policy documents are not exhaustive and are intended as a general reference.

• Examples of proprietary assay U-codes listed: 0206U (DISCERN™), 0207U (DISCERN™), 0289U (MindX Blood Test™), 0346U (QUEST AD-Detect™), 0358U (Lumipulse® G β-Amyloid Ratio), 0393U (SYNTap®).
• Providers must bill using the performing laboratory's information and verify coverage/payer billing rules.
• Procedure codes in policy are reference only and may not be all-inclusive.

Prior Authorization Not Specified in Reference Section

No explicit prior authorization codes or universal prior authorization requirements are specified within the bibliographic/reference section of this policy. Practitioners must verify authorization requirements with the payer for the specific plan and test.

• This policy does not provide universal prior authorization codes — check member-specific benefit and payer portals.
• Coverage and authorization may vary for FDA-cleared versus laboratory-developed tests (LDTs).

Analytic Variability Risk and Laboratory Quality Control

Analytic and preanalytical variability can affect plasma and other biomarker measurements, potentially leading to misclassification (false positives or false negatives). Laboratories should document standardization and quality control procedures due to between-laboratory variability.

• Plasma biomarker levels may be affected by small measurement variations from preanalytical handling and analytical performance.
• Document laboratory standardization/quality control and validation procedures (CLIA-certified high-complexity labs for LDTs).
• Alzheimer's Association quality control programs note large between-laboratory variability for CSF markers and recommend standardization.

Documentation Requirements When Ordering Biomarker Testing

Documentation submitted with biomarker testing requests should clearly support the clinical phenotype and rationale for testing (for example: persistent/progressive MCI, early-onset dementia, atypical presentation, or when results will change management). Include laboratory QC information for proprietary/LDT assays when applicable.

• Document the patient's clinical phenotype, objective testing results, and the specific clinical question the biomarker result will answer.
• Provide evidence of laboratory standardization/quality control when available (especially for LDTs or novel assays).
• Document intent (e.g., to confirm AD pathology to qualify for a clinical trial or to change therapeutic management).

Supporting Literature and Guideline Citations

This section provides citations and supporting literature for biomarker testing in Alzheimer's disease, including guideline recommendations and studies addressing diagnostic agreement, analytic considerations, and appropriateness of testing in specific clinical scenarios.

• Key references include Dubois et al. (2021), Shaw et al. (2018), Simonsen et al. (2017), and studies on analytic variability (Nojima et al., 2022).
• Guidelines emphasize limited, indication-driven use of biomarkers and note the current limitations of plasma biomarkers for routine clinical practice.

Stepwise Evaluation Prior to CSF Biomarker Testing

Stepwise evaluation before CSF testing is recommended: perform a complete clinical assessment and consider less invasive tests first. Use CSF biomarkers as an add-on to clinical evaluation or in comparison with imaging biomarkers when results will inform diagnosis or management.

• Evaluate clinical phenotype, cognitive testing, and structural imaging prior to biomarker testing.
• Consider PET imaging alternatives if lumbar puncture is contraindicated.
• Reserve biomarker testing for cases where results will alter management or support clinical trial eligibility.

Procedure Codes in Medical Policy — Reference Only

Procedure codes appearing in Medical Policy documents are included only as a general reference tool; they may not be all-inclusive. Providers should confirm current coding and billing practices with payers and laboratories.

• Reference codes include multiple U-codes for proprietary assays (see billing code reference callout).
• Providers are responsible for billing under the performing laboratory's NPI and for ensuring accurate test codes are used.

No Authorization or Denial Criteria Specified

There are no explicit authorization or denial criteria stated in the reference list section of this policy. Decisions about authorization or denial should be based on the payer's coverage rules, the member's benefit plan, and clinical documentation provided.

• Authorization or denial will be determined case-by-case per plan benefits and documented medical necessity.
• When in doubt, obtain prior authorization and supply supporting clinical documentation and lab validation data as applicable.