Blue Cross Blue Shield TN CSF Amyloid Coverage

Coverage Criteria for Biomarker Testing

Covered: CSF amyloid beta peptides

Covered when ALL of the following are met

Covered biomarker: Measurement of amyloid beta peptides in cerebrospinal fluid for individuals with Alzheimer disease or mild cognitive impairment meets coverage criteria.

Per policy indications and limitations of coverage.

Not covered: non-specified CSF biomarkers, plasma/serum, urine, multianalyte assays

The following do not meet coverage criteria

Not covered biomarker categories: Measurement of cerebrospinal fluid biomarkers not specified above (e.g., tau protein, α‑synuclein, neural thread proteins), measurement of plasma or serum biomarkers (e.g., tau, amyloid beta peptides, ApoE/ApoE4), measurement of urinary biomarkers (e.g., neural thread proteins, amyloid beta peptides, urinary extracellular vesicle analysis), and use of multianalyte assays or algorithmic/other tests not listed do not meet coverage criteria.

Explicit noncoverage list from policy 'Indications and/or Limitations of Coverage'.

Appropriate use indications for LP/CSF (Alzheimer's Association)

Alzheimer's Association 2018 recommendations rate lumbar puncture/CSF testing as appropriate or inappropriate for specific clinical indications:

Alzheimer's Association LP/CSF indications table: Table of 14 clinical indications with appropriateness ratings (examples): Indication 1 (cognitively unimpaired, no risk) = Inappropriate; Indication 2 (cognitively unimpaired but family history risk) = Inappropriate; Indication 3 (subjective cognitive decline with increased risk) = Appropriate; Indication 4 (SCD without increased risk) = Inappropriate; Indication 5 (persistent, progressive, unexplained MCI) = Appropriate; Indication 6 (symptoms suggesting possible AD) = Appropriate; Indication 7 (early‑onset <65) = Appropriate; Indication 8 (meets core clinical criteria for probable AD) = Appropriate; Indication 9 (REM sleep behavior disorder) = Inappropriate; Indication 10 (behavioral change dominant) = Appropriate; Indication 11 (determine disease severity after AD diagnosis) = Inappropriate; Indication 12 (APOE ɛ4 carriers with no impairment) = Inappropriate; Indications 13–14 = Inappropriate.

See Shaw et al., Alzheimer's Association appropriate use table (2018).

CSF biomarkers as add-on in MCI (JPND)

Expert working group recommendations for CSF biomarkers in MCI:

JPND BIOMARKAPD recommendations: Use CSF biomarkers as an add‑on to clinical evaluation in patients with MCI to predict functional decline or progression to Alzheimer disease dementia (recommendation strength: strong for prediction of conversion and decline); evidence for changing management is weaker.

Simonsen et al., JPND BIOMARKAPD (2017).

NIA-AA statements on biomarker utility and limitations

NIA-AA and related workgroups note biomarkers can support etiology and prognosis but are not yet recommended for routine clinical use and require harmonization and further study:

NIA-AA guidance: Biomarkers can help establish underlying etiology in MCI and estimate likelihood or timing of progression; combination of low CSF Aβ42 with elevated CSF tau confers a high likelihood of progression, but routine clinical use is not advocated pending further standardization, validation, and evidence and because biomarkers of neurodegeneration are nonspecific.

Albert et al., Jack et al.; NIA‑AA statements (2011, 2018).

Blood-based biomarkers (BBMs): recommended contexts

Alzheimer's Association recommendations for blood-based biomarkers (BBMs):

BBMs use contexts: Blood‑based biomarkers with established thresholds should currently only be used in symptomatic patients at specialist memory clinics and, when possible, results should be confirmed with CSF or PET; additional data are needed before BBMs are used as standalone diagnostics or in primary care.

Hansson et al., 2022 consensus statements on BBM implementation and caution for primary care use.

Selective Biomarker Use (CSF, PET, Plasma)

Covered when testing is expected to affect diagnosis or management and is used selectively in symptomatic patients with diagnostic uncertainty

Selective use in symptomatic patients: Biomarker investigations (CSF, PET) may be considered for symptomatic patients when results are expected to add diagnostic value or change management; decisions should account for age, comorbidity, phenotype complexity, patient preferences, and trial eligibility.

Dubois et al., IWG and guideline recommendations; NICE guidance on testing when it would change management.

Preferred modalities and alternatives: CSF investigation is prioritized because it provides simultaneous amyloid and tau data and is less expensive than PET; if lumbar puncture is contraindicated, PET is an alternative.

IWG/other guideline prioritization of CSF; PET as alternative when LP contraindicated.

Not recommended for asymptomatic screening: Investigation of pathophysiological biomarkers in cognitively unimpaired individuals is not recommended in routine clinical practice because they do not reliably predict clinical trajectory and testing is unlikely to benefit asymptomatic people.

The policy explicitly states that measurement of amyloid beta peptides in cerebrospinal fluid (CSF) for individuals with Alzheimer disease or mild cognitive impairment meets coverage criteria. Conversely, the policy lists that multianalyte assays, algorithmic analyses, and any other tests not specifically mentioned for prognosis, diagnosis, or management of Alzheimer disease or dementia do not meet coverage criteria. Examples given include non-specified CSF biomarkers, plasma/serum, and urine assays; these categories are not considered supported by sufficient published evidence and therefore are not covered.

Alzheimer's Association appropriate-use recommendations for lumbar puncture (LP)/CSF testing list multiple scenarios where LP/CSF testing is rated inappropriate, including cognitively unimpaired individuals without risk factors and certain other low-yield indications. The policy also emphasizes that blood-based biomarkers (BBMs) with established thresholds should currently be used only in symptomatic patients at specialist memory clinics and confirmed with CSF or PET when possible, underscoring restricted use outside those contexts.

Guideline summaries in the policy advise that biomarker assessments are not recommended for cognitively unimpaired individuals and that plasma or other peripheral biomarkers are not yet appropriate as standalone diagnostic tests in routine clinical practice. Biomarker results should be interpreted in the clinical context and used selectively when testing is expected to influence diagnosis or management; BBMs require specialist-clinic use with confirmatory CSF or PET when possible.

The policy includes a clear governing rule: when there is a conflict between this policy and any applicable government policy (for example, Medicare Local Coverage Determinations, National Coverage Determinations, or state Medicaid rules), the applicable government policy supersedes and will be used to make coverage determinations.

Within the excerpted material there are no additional explicit coverage exclusions beyond the listed non-covered biomarker categories and guideline-based limitations; the document primarily summarizes bibliographic and guideline recommendations rather than enumerating separate exclusionary services.

The policy notes that many proprietary blood tests and other peripheral biomarkers currently have limited clinical utility because standardization and validation are lacking. These assays—while commercially available or given regulatory designations—require further external validation and harmonization before broad clinical adoption is supported.

The Alzheimer's Association table specifically lists multiple indications where LP/CSF testing is inappropriate—for example, cognitively unimpaired individuals without risk factors and APOE ɛ4 carriers without impairment—making these scenarios low-yield for CSF biomarker evaluation and not recommended for routine use.

Professional guidance cited (NICE, IWG and others) states that routine CSF, PET, or plasma biomarker testing for screening or in circumstances where results will not change clinical management should generally be avoided. Further testing is recommended only when it would help establish a dementia subtype and where knowing the subtype would change management.

The provided excerpt does not include explicit statements labeling any services as universally Not Medically Necessary; rather, it distinguishes tests that meet coverage criteria from those that currently do not meet coverage criteria based on available evidence and guideline recommendations.

Coding and Procedure Codes

Applicable CPT/HCPCS procedure codes (group 1)mixed

83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
0206U	Neurology (Alzheimer disease); cell aggregation using morphometric imaging and protein kinase C-epsilon (PKCe) concentration in response to amylospheroid treatment by ELISA, cultured skin fibroblasts, each reported as positive or negative for Alzheimer disease Proprietary test: DISCERN™ Lab/Manufacturer: NeuroDiagnostics.
0207U	Quantitative imaging of phosphorylated ERK1 and ERK2 in response to bradykinin treatment by in situ immunofluorescence, using cultured skin fibroblasts, reported as a probability index for Alzheimer disease (List separately in addition to code for primary procedure) Proprietary test: DISCERN™ Lab/Manufacturer: NeuroDiagnostics.
0289U	Neurology (Alzheimer disease), mRNA, gene expression profiling by RNA sequencing of 24 genes, whole blood, algorithm reported as predictive risk score Proprietary test: MindX Blood Test™ - Memory/Alzheimer's Lab/Manufacturer: MindX Sciences™ Laboratory/MindX Sciences™ Inc.
0346U	Beta amyloid, Aβ40 and Aβ42 by liquid chromatography with tandem mass spectrometry (LC-MS/MS), ratio, plasma Proprietary test: QUEST AD-Detect™, Beta-Amyloid 42/40 Ratio, Plasma Lab/Manufacturer: Quest Diagnostics.
0358U	Neurology (mild cognitive impairment), analysis of β-amyloid 1-42 and 1-40, chemiluminescence enzyme immunoassay, cerebral spinal fluid, reported as positive, likely positive, or negative Proprietary test: Lumipulse® G β-Amyloid Ratio (1-42/1-40) Test

Applicable CPT/HCPCS procedure codes (group 2)mixed

0393U	Neurology (eg, Parkinson disease, dementia with Lewy bodies), cerebrospinal fluid (CSF), detection of misfolded α-synuclein protein by seed amplification assay, qualitative Proprietary test: SYNTap® Biomarker Test Lab/Manufacturer: Amprion Clinical Laboratory.
0412U	Beta amyloid, Aβ42/40 ratio, immunoprecipitation with quantitation by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and qualitative, ApoE isoform-specific proteotyping, plasma combined with age, algorithm reported as presence or absence of brain amyloid pathology Proprietary test: PrecivityAD® blood test Lab/Manufacturer: C2N Diagnostics LLC.
0443U	Neurofilament light chain (NfL), ultra-sensitive immunoassay, serum or cerebrospinal fluid Proprietary test: Neurofilament Light Chain (NfL) Lab/Manufacturer: Neuromuscular Clinical Laboratory at Washington University in St. Louis School of Medicine.
0445U	B-amyloid (abeta42) and phospho tau (181p) (ptau181), electrochemiluminescent immunoassay (eclia), cerebral spinal fluid, ratio reported as positive or negative for amyloid pathology Proprietary test: Elecsys® PhosphoTau (181P) CSF (pTau181) and βAmyloid (1-42) CSF II (Abeta 42) Ratio Lab/Manufacturer: Roche Diagnostics.
0459U	β-amyloid (Abeta42) and total tau (tTau), electrochemiluminescent immunoassay (ECLIA), cerebral spinal fluid, ratio reported as positive or negative for amyloid pathology Proprietary test: Elecsys® Total Tau CSF (tTau) and βAmyloid (1-42) CSF II (Abeta 42) Ratio Lab/Manufacturer: Roche Diagnostics.
0479U	Tau, phosphorylated, pTau217 Proprietary test: ALZpath pTau217 Lab/Manufacturer: Neurocode USA, Inc, Quanterix/ALZpath.
0503U	Neurology (Alzheimer disease), beta amyloid (Aβ40, Aβ42, Aβ42/40 ratio) and tau-protein (ptau217, np-tau217, ptau217/nptau217 ratio), blood, immunoprecipitation with quantitation by liquid chromatography with tandem mass spectrometry (LC-MS/MS), algorithm score reported as likelihood of positive or negative for amyloid plaques Proprietary test: PrecivityAD2™ Lab/Manufacturer: C2N Diagnostics, LLC.

inv-19: Age for certain FDA-cleared assays

Age restrictionAdults 55 years and older

Provider Actions, Documentation, and Billing Guidance

Prior Authorization

Use of BBMs in specialist clinics

Blood-based biomarkers (BBMs) should currently only be used in symptomatic patients evaluated in specialist memory clinics where established thresholds and expertise exist; results should be confirmed with cerebrospinal fluid (CSF) assays or amyloid PET whenever possible before major diagnostic or treatment decisions. Additional data are needed before BBMs are used as stand-alone diagnostic markers or in primary care.

Use BBMs only in specialist memory clinics for symptomatic patients with established thresholds.
Confirm positive BBM results with CSF or PET prior to major management changes (e.g., initiation of anti-amyloid therapy).
Do not use BBMs as standalone diagnostic tests or in primary care pending further validation.

Billing Rule

Applicable procedure codes — billing requirement

Background and Rationale

Alzheimer disease is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and neurofibrillary tangles and is the most common cause of dementia. Biomarker testing—particularly CSF measurement of amyloid beta peptides—is discussed in this policy as an adjunct to clinical evaluation in symptomatic patients and in selected circumstances to inform diagnosis and prognosis.

Definitions

inv-41: CSF — Cerebrospinal fluid

DefinitionCerebrospinal fluid (CSF)

inv-42: Aβ42/Aβ40 ratio — Ratio of amyloid beta 42 to amyloid beta 40, used as a CSF biomarker to detect amyloid pathology

DefinitionAβ42/Aβ40 ratio — Ratio of amyloid beta 42 to amyloid beta 40 used as a CSF biomarker to detect amyloid pathology

inv-43: MCI — Mild cognitive impairment

TermMCI — Mild cognitive impairment

inv-44: MCI — Mild cognitive impairment — a symptomatic stage between normal cognition and dementia where biomarkers may help predict progression

OpenPayer

Biochemical Markers of Alzheimer Disease and Dementia — Coverage Criteria

Coverage Criteria for Biomarker Testing

Coding and Procedure Codes

Provider Actions, Documentation, and Billing Guidance

Background and Rationale

Definitions