Can blood tests diagnose Alzheimer's disease?

Blood Tests for Alzheimer's Disease Diagnosis

Blood-based biomarkers (BBMs) for Alzheimer's disease should be used cautiously in specialized memory clinics as part of the diagnostic workup of patients with cognitive symptoms, but they are not yet validated for use as stand-alone diagnostic tests and require confirmation with cerebrospinal fluid (CSF) or positron emission tomography (PET) whenever possible. 1

Current Status of Blood-Based Biomarkers for Alzheimer's Disease

Promising Biomarkers

• Plasma phosphorylated tau (p-tau) variants, particularly p-tau181, p-tau217, and p-tau231, have shown high diagnostic accuracy for separating Alzheimer's disease from other neurodegenerative diseases 1
• The combination of plasma p-tau and amyloid-β 42:40 ratio (Aβ42:Aβ40) has demonstrated strong performance in detecting AD pathology 2
• Recent research shows that the amyloid probability score 2 (APS2), which combines p-tau217 and Aβ42:Aβ40 measurements, achieves high diagnostic accuracy (88-92%) in both primary and secondary care settings 2

Current Limitations

• Blood-based biomarkers are not yet validated for use as stand-alone diagnostic tests for Alzheimer's disease 1
• Additional research is needed before widespread implementation, particularly in primary care settings 1
• Pre-analytical protocols and standardization of blood sample collection and processing need further refinement 1

Appropriate Use Recommendations

Specialized Memory Clinics

• BBMs may be cautiously used in specialized memory clinics as part of the diagnostic workup of patients with cognitive symptoms 1
• Results from blood tests should be confirmed whenever possible with CSF or PET 1
• BBMs should be used as an adjunct to, not a substitute for, a thorough clinical evaluation 1

Primary Care Settings

• BBMs are not yet recommended for routine use in primary care settings 1
• No studies have extensively evaluated BBMs for neurodegenerative diseases in primary care 1
• The patient population with cognitive symptoms in primary care is more heterogeneous with more frequent comorbidities and co-pathologies than in specialized memory clinics 1

Clinical Trials

• BBMs are recommended as pre-screeners to identify individuals likely to have AD pathological changes for inclusion in trials evaluating disease-modifying therapies 1
• AD status should be confirmed with PET or CSF testing 1
• Longitudinal BBM changes should be studied in ongoing and future interventional trials 1

Diagnostic Performance and Implementation

Recent Evidence

• A 2024 study demonstrated that plasma p-tau217 testing, alone or combined with Aβ42:Aβ40 ratio (APS2), achieved high diagnostic accuracy (90%) for identifying AD among individuals with cognitive symptoms in both primary and secondary care 2
• Primary care physicians' diagnostic accuracy for identifying clinical AD improved from 61% using standard clinical examination to 91% when using the APS2 blood test 2
• Dementia specialists' diagnostic accuracy improved from 73% to 91% when using the APS2 blood test 2

Implementation Considerations

• Standardized protocols for blood sample collection, processing, and storage are essential for reliable results 1
• According to current protocols, samples can be stored in a refrigerator (2-8°C) for 24 hours before centrifugation, and another 24 hours before being analyzed or frozen 1
• Clinical-grade assays with high precision and analytical stability are critical for real-world implementation 1

Research Priorities

Clinical Validation

• Evaluation of BBMs in diverse real-life memory clinic populations using prospective studies with predefined cut-offs and accurate reference standards 1
• Identification of optimal combinations of easily accessible and cost-effective biomarkers and tests in memory clinic settings 1
• Determination of whether certain BBM-based algorithms can be used alone to support an AD diagnosis or should only be used as a gatekeeper to CSF/PET 1

Primary Care Implementation

• Prospective studies in primary care settings, including representative and diverse populations with cognitive symptoms 1
• Identification of optimal combinations of BBMs with other easily accessible and scalable tools in primary care 1
• Studies to determine whether BBMs outperform current standard of care in primary care and improve diagnosis and management 1

Common Pitfalls to Avoid

• Relying solely on blood tests without comprehensive clinical assessment 1, 3
• Failing to confirm blood test results with CSF or PET when possible 1
• Overlooking medical conditions that can influence biomarker interpretation, such as obesity or chronic kidney disease 3
• Using BBMs in asymptomatic individuals outside of research settings 1