Is there a reliable blood test to diagnose Alzheimer's disease in a geriatric patient?

Blood Tests for Alzheimer's Disease: Clinical Reliability

Yes, blood tests for Alzheimer's disease are now clinically reliable and available, particularly for detecting amyloid pathology, though they should not be used as standalone diagnostic tools and must be interpreted within the appropriate clinical context. 1

Current Clinical Status

Blood-based biomarkers (BBM) have reached a significant milestone in Alzheimer's disease diagnosis:

• Multiple blood tests are now clinically available and widely used in AD research studies and clinical trials, with the first commercially available test introduced in 2020 by C2N Diagnostics. 1

• The most promising blood biomarkers for detecting amyloid pathology include the Aβ42/Aβ40 ratio and phosphorylated tau at different sites (p-tau181, p-tau217, and p-tau231). 2

• P-tau217 assays demonstrate exceptional performance, with receiver operating characteristic area under the curve (AUC) values of 0.92–0.98, which is comparable to CSF tests for classifying amyloid PET status. 2, 1

• FDA-approved anti-amyloid drugs (lecanemab, donanemab) require confirmation of brain amyloidosis before treatment initiation, and the prescribing information for lecanemab does not specify the biomarker testing modality, leaving open the option of using blood tests. 2

Performance Standards for Clinical Use

The reliability of blood tests depends on their intended clinical application:

As a Triaging/Screening Test:

• Sensitivity ≥90% with specificity ≥85% in primary care settings is required. 1
• Sensitivity ≥90% with specificity ≥75–85% in secondary care settings is acceptable. 1
• This allows blood tests to identify patients who need confirmatory testing with amyloid PET or CSF analysis. 1

As a Confirmatory Test:

• Sensitivity and specificity of approximately 90% (equivalent to CSF tests) is required for use without follow-up testing. 1
• P-tau217 assays currently meet this threshold. 2, 1

Critical Limitations and Caveats

Despite their promise, several important limitations exist:

• Blood biomarkers cannot serve as standalone diagnostic tests for symptomatic AD, as cognitive symptoms often have multiple causes. 2

• Wide variation in test performance exists even among tests measuring the same analyte, depending on assay type (mass spectrometry versus immunoassay), antibodies used, and specific platform. 2

• Lack of standardization in blood sample collection, processing, storage, and analysis affects reproducibility of measurements. 2, 1

• No certified reference measurement procedures currently exist for blood-based AD biomarkers. 2

• Blood tests are currently limited to research use in many settings, though some are CLIA-certified; they are not yet FDA-approved or covered by most payers. 2

Clinical Algorithm for Use

For geriatric patients with cognitive concerns:

1. Perform comprehensive clinical evaluation to establish whether symptoms are consistent with AD clinical syndrome and rule out alternative causes. 2

2. Order blood biomarker testing (preferably p-tau217 or p-tau217/tau ratio) if:

   • Clinical syndrome suggests AD
   • Patient is being considered for anti-amyloid therapy
   • Access to PET or CSF testing is limited 2, 1

3. Interpret results in clinical context:

   • Positive blood test + typical AD syndrome = high likelihood of AD pathology 3
   • Consider confirmatory testing with amyloid PET or CSF if treatment decisions depend on it 1
   • Negative blood test with high clinical suspicion warrants further evaluation 1

4. Ensure samples are shipped to centralized laboratories with proper collection and storage protocols, as point-of-care testing is not yet available. 1

Advantages Over Traditional Biomarkers

Blood tests offer substantial practical benefits:

• More acceptable to patients and less invasive than lumbar puncture for CSF collection. 2

• More accessible and scalable than amyloid PET (which costs approximately $8,000 per scan) or CSF testing. 2

• Can be performed in primary care settings, enabling earlier detection and referral. 1

• No specialized personnel or equipment required for blood collection, though proper handling protocols must be followed. 2

Key Pitfalls to Avoid

• Do not use blood tests alone without clinical evaluation – this carries significant risk of misinterpretation. 4

• Do not assume all blood tests perform equally – p-tau217 assays significantly outperform Aβ42/Aβ40 ratio tests (AUC 0.92–0.98 versus 0.70–0.85). 2

• Do not order blood tests in asymptomatic individuals without appropriate counseling about implications of results. 4

• Ensure proper pre- and post-test counseling is provided, as with any biomarker testing. 4