TL;DR: Aetna, a CVS Health company, modified CPB 0349 covering Alzheimer's disease diagnostic tests, effective December 20, 2025. Billing teams managing CSF biomarker panels, brain MRI monitoring for anti-amyloid therapies, and genetic testing need to review criteria now.
This Aetna Alzheimer's disease coverage policy governs a wide range of diagnostic codes—from lumbar puncture (CPT 62270) and CSF biomarker assays (CPT 0412U, 0479U, 0503U, 0551U, 0568U) to brain MRI series (CPT 70551–70553) and ApoE4 genetic testing (HCPCS S3852). The policy sits at the intersection of three expensive drug therapies—Aduhelm, Leqembi, and Kisunla—and the diagnostic work required before and during treatment. If your practice or lab bills for Alzheimer's workups on Aetna members, CPB 0349 in the Aetna system is the document that controls whether those claims pay or deny.
| Field | Detail |
|---|---|
| Payer | Aetna, a CVS Health company |
| Policy | Alzheimer's Disease Tests — CPB 0349 |
| Policy Code | CPB 0349 |
| Change Type | Modified |
| Effective Date | December 20, 2025 |
| Impact Level | High |
| Specialties Affected | Neurology, Geriatric Psychiatry, Clinical Laboratory, Radiology, Genetic Counseling, Revenue Cycle |
| Key Action | Audit charge capture for CSF biomarker assays, brain MRI monitoring sequences, and genetic testing codes against the updated criteria before billing post–December 20, 2025 claims |
Aetna Alzheimer's Disease Test Coverage Criteria and Medical Necessity Requirements 2025
Aetna's Alzheimer's disease coverage policy draws a sharp line between tests that meet medical necessity and tests that are flat experimental. The covered side is narrower than many billing teams assume—and it ties directly to specific drug therapies.
CSF Biomarkers via Lumbar Puncture
Aetna covers lumbar puncture (CPT 62270) to confirm CSF biomarkers when Alzheimer's disease is suspected in a patient with mild cognitive impairment (MCI). The policy requires detection of at least one of the following:
| # | Covered Indication |
|---|---|
| 1 | Elevated phosphorylated tau (P-tau) and/or elevated total tau (T-tau), plus reduced beta-amyloid-42 (AB42) |
| 2 | Low AB42/AB40 ratio |
| 3 | Elevated P-tau/AB42 ratio |
| 4 | Elevated T-tau/AB42 ratio |
The CSF assay codes that fall under this coverage path include CPT 82233 (Abeta 1-40), 82234 (Abeta 1-42), 84393 (phosphorylated tau), and 84394 (total tau). Proprietary assay codes 0358U, 0445U, and 0459U are also covered when criteria are met.
Two important carve-outs: CPT 82233, 82234, 84393, and 84394 are explicitly not covered for plasma testing—only CSF. If your lab bills these codes on a blood draw, expect a claim denial.
Brain MRI Monitoring During Anti-Amyloid Therapy
This is where the coverage policy gets specific and where billing errors tend to pile up. Aetna covers brain MRI (CPT 70551, 70552, 70553) for Aetna members on Aduhelm, Leqembi, or Kisunla under two conditions:
| # | Covered Indication |
|---|---|
| 1 | One MRI within the year before starting therapy, to confirm AD diagnosis |
| 2 | Monitoring MRIs to evaluate for ARIA (amyloid-related imaging abnormalities) at specific dose intervals |
The dose-interval requirements differ by drug:
| # | Covered Indication |
|---|---|
| 1 | Aduhelm: Prior to the 5th, 7th, 9th, and 12th dose |
| 2 | Leqembi: Prior to the 5th, 7th, and 14th dose |
| 3 | Kisunla: Prior to the 2nd, 3rd, 4th, and 7th dose |
Build dose-tracking into your workflow before December 20, 2025. Note: prior authorization requirements, if any, are governed by Aetna's separate utilization management processes—not by CPB 0349 itself. Check with your Aetna provider relations contact for PA requirements specific to your plan contracts.
Genetic Testing
Aetna covers two types of genetic testing under this policy. Both are conditional on specific clinical contexts.
APP/PSEN1/PSEN2 mutation testing (CPT 81401, 81405, 81406) is covered for members with MCI or mild AD dementia who are under 50 years old and being considered for Aduhelm or Leqembi therapy. For Aduhelm, the member must also be enrolled in a clinical trial.
ApoE4 testing (HCPCS S3852) is covered for members with MCI or mild AD dementia being considered for any of the three anti-amyloid drugs—Aduhelm, Leqembi, or Kisunla. The Aduhelm clinical trial enrollment requirement applies here too.
Both tests require medical necessity documentation that ties explicitly to drug candidacy. A genetic test ordered for general risk assessment or family history will not meet criteria.
Aetna Alzheimer's Disease Test Exclusions and Non-Covered Indications
The experimental list in CPB 0349 is long—and it includes several codes your lab may already bill. Aetna classifies the following as experimental, investigational, or unproven for Alzheimer's diagnosis or management:
| # | Excluded Procedure |
|---|---|
| 1 | AI and machine learning applications for cognitive assessment |
| 2 | Automated computerized cognitive assessment aids |
| 3 | Blood-based neurodegenerative analytes used as AD biomarkers—including cholesterol (CPT 82465), ferritin (CPT 82728), iron (CPT 83540), triglycerides (CPT 84478), homocysteine (CPT 83090), natriuretic peptide (CPT 83880), and IGF-1/somatomedin (CPT 84305). These are all listed under CPB 0349 as not covered for this indication. |
| 4 | Plasma tau and beta-amyloid panels—the PLA codes 0412U, 0479U, 0503U, 0551U, 0568U, and 0596U are listed in the non-covered group. This is a significant exclusion given how many commercial labs are now marketing these panels. |
| 5 | Plasma ApoE isoform testing (CPT 0596U) |
| 6 | CSF prion protein, alpha-synuclein, golgin A4, microRNAs, synaptic biomarkers, and stathmin are all non-covered |
| 7 | Vestibular function testing (CPT 92540–92570) when ordered as an AD diagnostic |
| 8 | Retinal imaging (CPT 92134) for AD screening |
| 9 | Circadian rhythm analysis, cognitive evoked potentials, electronystagmography, olfactory testing, skin biopsy for phosphorylated alpha-synuclein, sleep polysomnography—all experimental under this policy |
| 10 | ApoE testing for any indication not specifically listed in the covered criteria |
The real issue here is plasma biomarker panels. Several new PLA codes—including 0412U (AB42/40 ratio by LC-MS/MS), 0479U (pTau217), 0503U (multi-analyte AD panel), 0551U (pTau217 by Simoa), and 0568U (dementia panel)—are grouped as non-covered under CPB 0349. These are actively being marketed to neurologists as blood-based alternatives to lumbar puncture. Aetna's position as of December 20, 2025 is that they don't meet medical necessity standards. If you're billing these codes on Aetna claims, you need to know that now.
Coverage Indications at a Glance
| Indication | Status | Relevant Codes | Notes |
|---|---|---|---|
| Lumbar puncture for CSF biomarker confirmation in MCI/AD workup | Covered | CPT 62270, 82233, 82234, 84393, 84394, 0358U, 0445U, 0459U, 82542, 83520 | Specific ratio/level criteria must be met; CSF only—not plasma |
| Brain MRI within 1 year prior to starting Aduhelm, Leqembi, or Kisunla | Covered | CPT 70551, 70552, 70553 | Must document AD indication |
| Brain MRI for ARIA monitoring during Aduhelm therapy | Covered | CPT 70551, 70552, 70553 | Required prior to doses 5, 7, 9, and 12 |
| Brain MRI for ARIA monitoring during Leqembi therapy | Covered | CPT 70551, 70552, 70553 | Required prior to doses 5, 7, and 14 |
| Brain MRI for ARIA monitoring during Kisunla therapy | Covered | CPT 70551, 70552, 70553 | Required prior to doses 2, 3, 4, and 7 |
| APP/PSEN1/PSEN2 genetic mutation testing | Covered | CPT 81401, 81405, 81406 | Age < 50, MCI or mild AD, Aduhelm or Leqembi candidacy; Aduhelm requires clinical trial enrollment |
| ApoE4 testing for anti-amyloid drug candidacy | Covered | HCPCS S3852 | MCI or mild AD; Aduhelm requires clinical trial enrollment |
| Plasma beta-amyloid and tau panels (0412U, 0479U, 0503U, 0551U, 0568U) | Not Covered / Experimental | CPT 0412U, 0479U, 0503U, 0551U, 0568U | Blood-based panels not meeting medical necessity criteria |
| Blood neurodegenerative analytes as AD biomarkers | Not Covered / Experimental | CPT 82465, 82728, 83540, 84478, 83090, 83880, 84305, 82530, 82533 | Cholesterol, ferritin, iron, triglycerides, homocysteine, etc. |
| Plasma ApoE isoform testing | Not Covered / Experimental | CPT 0596U | ApoE4 only covered via S3852 under specific criteria |
| AI/ML cognitive assessment applications | Not Covered / Experimental | CPT 0206U, 0207U, 0289U | All AI/ML-based tools classified as experimental |
| Vestibular testing as AD diagnostic | Not Covered / Experimental | CPT 92540–92570, 92550 | Experimental for this indication |
| Retinal imaging for AD screening | Not Covered / Experimental | CPT 92134 | Experimental for this indication |
| CSF alpha-synuclein, synaptic biomarkers, prion protein, microRNAs | Not Covered / Experimental | CPT 0393U | Experimental for AD assessment |
| ApoE testing for indications other than drug candidacy | Not Covered / Experimental | CPT 82172 | General risk assessment not covered |
Aetna Alzheimer's Disease Billing Guidelines and Action Items 2025
Note: CPB 0349 defines medical necessity criteria—it does not specify prior authorization requirements. Prior authorization requirements, if any, are governed by Aetna's separate utilization management processes. Contact your Aetna provider relations representative to confirm PA requirements for your specific plan contracts before the December 20, 2025 effective date.
| # | Action Item |
|---|---|
| 1 | Audit your CSF biomarker claims before billing any post–December 20, 2025 dates of service. Confirm that CPT 82233, 82234, 84393, and 84394 are tied to CSF collection—not blood draws. Add a modifier or note in your charge capture system flagging these codes as CSF-only. |
| 2 | Remove plasma biomarker PLA codes from Aetna charge masters if they're currently set to bill. CPT codes 0412U, 0479U, 0503U, 0551U, 0568U, and 0596U are all classified as non-covered under this coverage policy. Billing them on Aetna claims will generate denials. If your lab is performing these tests, discuss with your ordering providers whether CSF-based alternatives are appropriate for Aetna members. |
| 3 | Build dose-tracking into your MRI workflow for all three anti-amyloid therapies. CPB 0349 ties MRI coverage (CPT 70551–70553) to specific dose numbers. Set up a tracking mechanism in your EHR or workflow so your team knows which dose the patient is approaching before submitting any documentation. Contact Aetna's utilization management team separately to confirm whether PA is required for these MRIs under your specific contracts. |
| 4 | Verify age and drug candidacy before billing APP/PSEN1/PSEN2 genetic tests. CPT 81401, 81405, and 81406 are only covered for members under 50. If the patient is 50 or older, Aetna's Alzheimer's disease billing guidelines don't support coverage under this policy—document the age clearly in the medical record. |
| 5 | Flag Aduhelm orders for clinical trial enrollment verification. Both genetic testing (CPT 81401, 81405, 81406) and ApoE4 testing (HCPCS S3852) for Aduhelm therapy require clinical trial enrollment. This is a hard criterion. A claim without documentation of enrollment will not survive appeal. |
| 6 | Review your denial queue for blood-based analyte codes billed for AD indications. CPT 82465, 82728, 83540, 84478, 83090, and 84305 may be billing legitimately for other indications—but if your coders are appending Alzheimer's ICD-10 codes (G30.0, G30.1, or the F01–F03 range), expect denials under CPB 0349. |
| 7 | If your practice offers AI-assisted cognitive testing tools, do not bill them on Aetna claims for AD diagnosis. CPT 0206U, 0207U, and 0289U fall in the experimental group. Talk to your compliance officer before the effective date if you're unsure how your current cognitive assessment workflow maps to these codes. |
| Previous Version | Current Version |
|---|---|
| Coverage is considered experimental and investigational for all indications | Coverage is considered medically necessary when specific criteria are met |
| Prior authorization is not required | Prior authorization is required for initial treatment |
| Documentation must include clinical history | Documentation must include clinical history |
| Re-review every 24 months | Re-review every 12 months with updated clinical documentation |
CPT, HCPCS, and ICD-10 Codes for Alzheimer's Disease Tests Under CPB 0349
Covered CPT Codes (When Selection Criteria Are Met)
| Code | Type | Description |
|---|---|---|
| 0358U | CPT | Neurology (mild cognitive impairment), analysis of B-amyloid 1-42 and 1-40, chemiluminescence enzyme immunoassay (CLIA) |
| 0445U | CPT | β-amyloid (Abeta42) and phospho tau (181P) (pTau181), electrochemiluminescent immunoassay (ECLIA), CSF |
| 0459U | CPT | B-amyloid (Abeta42) and total tau (tTau), electrochemiluminescent immunoassay (ECLIA), CSF |
| 62270 | CPT | Spinal puncture, lumbar, diagnostic |
| 70551 | CPT | MRI brain without contrast material |
| 70552 | CPT | MRI brain with contrast material(s) |
| 70553 | CPT | MRI brain without contrast, followed by contrast material(s) and further sequences |
| 81401 | CPT | Molecular pathology procedure, Level 2 |
| 81405 | CPT | Molecular pathology procedure, Level 6 — PSEN1 full gene sequence |
| 81406 | CPT | Molecular pathology procedure, Level 7 — APP full gene sequence |
| 82233 | CPT | Beta-amyloid; 1-40 (Abeta 40) — CSF only, not plasma |
| 82234 | CPT | Beta-amyloid; 1-42 (Abeta 42) — CSF only, not plasma |
| 82542 | CPT | Column chromatography, includes mass spectrometry, if performed |
| 83520 | CPT | Immunoassay for analyte other than infectious agent antibody or antigen; quantitative |
| 84393 | CPT | Tau, phosphorylated (pTau 181, pTau 217), each — CSF only, not plasma |
| 84394 | CPT | Tau, total (tTau) — CSF only, not plasma |
Not Covered / Experimental CPT Codes
| Code | Type | Description | Reason |
|---|---|---|---|
| 0206U | CPT | Neurology (Alzheimer disease); cell aggregation using morphometric imaging and protein kinase C-epsilon | AI/ML and experimental assay |
| 0207U | CPT | Disease quantitative imaging of phosphorylated ERK1 and ERK2 in response to bradykinin treatment | AI/ML and experimental assay |
| 0289U | CPT | Neurology (Alzheimer disease), mRNA, gene expression profiling by RNA sequencing of 24 genes | Experimental |
| 0393U | CPT | Neurology (dementia), CSF, detection of prion protein | Experimental |
| 0412U | CPT | Beta amyloid, AB42/40 ratio, immunoprecipitation with quantitation by LC-MS/MS | Plasma biomarker — experimental |
| 0479U | CPT | Tau, phosphorylated, pTau217 | Plasma biomarker — experimental |
| 0503U | CPT | Neurology (Alzheimer disease), beta amyloid and tau-protein (ptau217, np-tau217) | Plasma biomarker — experimental |
| 0551U | CPT | Tau, phosphorylated, pTau217, by single-molecule array (Simoa) | Plasma biomarker — experimental |
| 0568U | CPT | Neurology (dementia), beta amyloid (AB40, AB42, AB42/40 ratio), tau-protein phosphorylated | Plasma biomarker — experimental |
| 0596U | CPT | Neurology (Alzheimer disease), plasma, 3 distinct isoform-specific APOE peptides | Plasma ApoE isoform — experimental |
| 82172 | CPT | Apolipoprotein, each | ApoE for non-covered indications |
| 82465 | CPT | Cholesterol, serum or whole blood, total | Blood neurodegenerative analyte — experimental for AD |
| 82530 | CPT | Cortisol; free | Long-term cortisol measurement — experimental |
| 82533 | CPT | Cortisol; total | Long-term cortisol measurement — experimental |
| 82728 | CPT | Ferritin | Blood neurodegenerative analyte — experimental for AD |
| 83090 | CPT | Homocysteine | Blood neurodegenerative analyte — experimental for AD |
| 83540 | CPT | Iron | Blood neurodegenerative analyte — experimental for AD |
| 83880 | CPT | Natriuretic peptide | Blood biomarker — experimental for AD |
| 83884 | CPT | Neurofilament light chain (NfL) | Experimental for AD |
| 84305 | CPT | Somatomedin (IGF-1) | Blood neurodegenerative analyte — experimental for AD |
| 84478 | CPT | Triglycerides | Blood neurodegenerative analyte — experimental for AD |
| 86777 | CPT | Antibody; Toxoplasma | Experimental for AD assessment |
| 86778 | CPT | Antibody; Toxoplasma, IgM | Experimental for AD assessment |
| 92134 | CPT | Scanning computerized ophthalmic diagnostic imaging, posterior segment | Retinal imaging — experimental for AD |
| 92540 | CPT | Basic vestibular evaluation | Experimental for AD diagnosis |
| 92541 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92542 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92543 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92544 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92545 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92546 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92547 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92548 | CPT | Vestibular function tests, with recording | Experimental for AD diagnosis |
| 92550 | CPT | Tympanometry and reflex threshold measurements | Experimental for AD diagnosis |
| 92567 | CPT | Tympanometry (impedance testing) | Experimental in absence of hearing loss — AD context |
| 92568 | CPT | Acoustic reflex testing | Experimental in absence of hearing loss — AD context |
| 92569 | CPT | Acoustic reflex testing | Experimental in absence of hearing loss — AD context |
| 92570 | CPT | Acoustic immittance testing | Experimental for AD diagnosis |
Other CPT Codes Related to CPB 0349
| Code | Type | Description |
|---|---|---|
| 78608 | CPT | Brain imaging, PET; metabolic evaluation |
| 88271 | CPT | Molecular cytogenetics |
| 88272 | CPT | Molecular cytogenetics |
| 88273 | CPT | Molecular cytogenetics |
| 88274 | CPT | Molecular cytogenetics |
| 88275 | CPT | Molecular cytogenetics |
HCPCS Codes Under CPB 0349
| Code | Type | Description | Status |
|---|---|---|---|
| S3852 | HCPCS | DNA analysis for APOE epsilon 4 allele for susceptibility to Alzheimer's disease | Covered when criteria met |
| A9586 | HCPCS | Florbetapir F18, diagnostic, per study dose, up to 10 millicuries | Related — see CPB 0071 |
| A9598 | HCPCS | PET radiopharmaceutical, diagnostic, non-tumor identification | Related — see CPB 0071 |
| J0172 | HCPCS | Injection, aducanumab-avwa (Aduhelm), 2 mg | Related — see CPB 0996 |
| J0174 | HCPCS | Injection, lecanemab-irmb (Leqembi), 1 mg | Related — see CPB 1026 |
| J0175 | HCPCS | Injection, donanemab-azbt (Kisunla), 2 mg | Related — see CPB 1066 |
| Q9982 | HCPCS | Flutemetamol F18, diagnostic, per study dose, up to 5 millicuries | Related — see CPB 0071 |
Key ICD-10-CM Diagnosis Codes
| Code | Description |
|---|---|
| F01.50–F03.C4 | Dementia (for members under age 50 for genetic testing criteria) |
| F07.0–F07.9 | Personality and behavioral disorders due to known physiological condition |
| G30.0 | Alzheimer's disease |
| G30.1 | Alzheimer's disease |
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