What blood test is used for Alzheimer’s disease screening in adults aged 65 and older?

Blood Tests for Alzheimer's Disease Screening

Blood-based biomarker (BBM) tests measuring plasma phosphorylated tau (particularly p-tau217, p-tau181, p-tau231) and the Aβ42/Aβ40 ratio are now used for Alzheimer's disease screening in adults aged 65 and older with cognitive impairment, though these tests are NOT recommended as standalone screening tools in asymptomatic individuals. 1, 2

Critical Context: When Blood Tests Should Be Used

Blood biomarker testing is only appropriate after comprehensive clinical evaluation in patients who already have cognitive symptoms. This means:

• Medical evaluation and neurological examination completed
• Cognitive testing performed
• Laboratory testing for reversible causes of cognitive impairment ruled out (thyroid disease, B12 deficiency, etc.)
• Patient has documented mild cognitive impairment or mild dementia

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Key caveat: No AD biomarker test—blood, CSF, or imaging—is intended as a standalone diagnostic test. Multiple conditions cause cognitive impairment, and the comprehensive assessment identifies these alternative causes first. 1

Specific Blood Tests Available

The most clinically validated blood biomarkers include:

Highest Performance Tests:

• Plasma p-tau217 (AUC 0.92-0.98 for detecting amyloid pathology)
• Plasma %p-tau217 (ratio of phosphorylated-tau217 to non-phosphorylated tau)
• Plasma pTau217/Aβ1-42 ratio - FDA-cleared as of May 2025 (Lumipulse G test with 91.7% positive and 97.3% negative concordance with amyloid PET) 3, 4

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Other Validated Markers:

• Plasma p-tau181 (moderate-high performance)
• Plasma p-tau231 (moderate-high performance)
• Plasma Aβ42/Aβ40 ratio (AUC 0.70-0.85, lower than p-tau markers)

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Performance Hierarchy

P-tau217 assays demonstrate superior accuracy compared to other blood biomarkers, with performance clinically equivalent or superior to FDA-approved CSF tests. Mass spectrometry-based assays typically outperform immunoassays for the same analyte. 5

In cognitively impaired patients, plasma %p-tau217 achieved:

• 89-90% accuracy for amyloid PET status
• 87-88% accuracy for tau PET status
• Improved to 95% accuracy using a two-cutoff approach

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Clinical Application Algorithm

Step 1: Patient presents with cognitive complaints → Complete comprehensive evaluation (medical, neurological, cognitive testing, reversible causes ruled out)

Step 2: If cognitive impairment confirmed → Blood biomarker testing appropriate (p-tau217 preferred given highest accuracy)

Step 3: Positive blood test → Confirms amyloid pathology present; patient may be candidate for disease-modifying therapies (lecanemab, donanemab)

Step 4: Negative blood test → Amyloid pathology unlikely; consider alternative dementia etiologies

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Important Limitations and Pitfalls

Do NOT use blood biomarkers for:

• Screening asymptomatic individuals (not validated, raises ethical concerns about psychological burden) 4
• Standalone diagnosis without clinical evaluation 1
• Replacing comprehensive dementia workup

Technical considerations:

• Different assays measuring the same analyte (e.g., p-tau217) have varying performance based on technology platform and antibodies used 1
• Blood must be collected and stored under appropriate conditions 1
• Test performance varies by clinical setting and pretest probability 2

Interpretation challenges:

• Blood biomarkers primarily detect amyloid pathology, which correlates with but does not perfectly predict symptomatic AD 6
• Positive amyloid biomarkers can occur in cognitively normal individuals
• Some biomarkers (GFAP) may be influenced by vascular risk factors 7

Advantages Over Traditional Testing

Blood tests offer significant practical benefits compared to CSF analysis (lumbar puncture) and amyloid PET imaging:

• Less invasive and more acceptable to patients
• Lower cost than PET imaging
• More scalable (no specialized personnel or equipment required)
• Wider accessibility in clinical practice
• Can be performed in specialized care settings now, with primary care applications under development

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Current Regulatory Status

The FDA cleared its first blood-based AD test (Lumipulse G measuring pTau217/Aβ1-42 ratio) in May 2025 for diagnosis of amyloid plaques in symptomatic patients age 55 or older. 3, 4 The prescribing information for lecanemab (disease-modifying therapy) does not specify biomarker testing modality, leaving blood biomarker testing as an acceptable option. 1