Is there a blood test for diagnosing Alzheimer's disease?

Blood Tests for Alzheimer's Disease

Yes, blood tests for Alzheimer's disease are now available and show promising accuracy in detecting amyloid pathology, though they are still evolving as diagnostic tools. 1

Current Status of Blood-Based Biomarkers

• Blood-based biomarker tests for Alzheimer's disease have advanced significantly in recent years, with multiple tests becoming clinically available and widely used in research studies and clinical trials 1
• A milestone was reached in 2020 when the first commercially available blood test for detecting brain amyloid plaque was introduced by C2N Diagnostics 1
• The most promising blood biomarkers for detecting amyloid status include:
  • Amyloid-beta (Aβ) 42/40 ratio 2, 1
  • Phosphorylated tau at different sites (p-tau181, p-tau217, p-tau231) 2, 1
  • Neurofilament light chain (NfL) 2, 1
  • Glial fibrillary acidic protein (GFAP) 2, 1

Performance of Blood Tests

• Plasma p-tau217 tests show particularly strong performance with AUCs (area under the curve) of 0.92-0.98, comparable to cerebrospinal fluid (CSF) tests for classifying amyloid PET status 2, 1
• Mass spectrometry-based assays of the plasma Aβ42/40 ratio typically show AUCs of 0.70-0.85 and are generally more accurate than immunoassays 2
• For clinical use as a triaging test before confirmatory tests, blood biomarker tests should have:
  • Sensitivity ≥90% with specificity ≥85% in primary care settings 1
  • Sensitivity ≥90% with specificity ≥75-85% in secondary care 1
• For use as a standalone confirmatory test, performance should be equivalent to CSF tests (approximately 90% sensitivity and specificity) 1

Advantages Over Traditional Methods

• Blood tests are less invasive, more acceptable to patients, and more accessible than traditional biomarker testing methods 1, 3
• They are significantly more cost-effective than amyloid PET scans, which can cost at least $8,000 per participant in clinical trials 2
• Blood collection doesn't require highly specialized personnel or equipment, allowing for easier scaling up compared to PET imaging or CSF collection 2, 1
• Blood tests could potentially be performed in primary care and community-based settings, enabling widespread screening 1

Current Limitations and Challenges

• Lack of standardization in blood sample collection, processing, storage, and analysis affects reproducibility of biomarker measurements 2, 1
• Different blood tests have widely varying performances for classification of amyloid status, even when designed to measure the same analyte 2
• Most blood tests currently require samples to be shipped to centralized laboratories for analysis 1
• Technical performance, diagnostic accuracy, and prognostic value across diverse populations still need further validation 1
• Blood tests are not yet intended as standalone diagnostic tests for symptomatic AD, as cognitive symptoms often have multiple causes 2

Clinical Implementation Path

• Recent FDA-approved anti-amyloid drugs like lecanemab require confirmation of brain amyloidosis before treatment initiation, making accurate blood biomarkers valuable 2, 1
• Blood biomarkers could serve as pre-screening measures to identify individuals who should undergo more definitive testing with PET or CSF analysis 2, 1
• The 2024 revised criteria for diagnosis of Alzheimer's disease by the Alzheimer's Association Workgroup recognize that accurate plasma biomarkers (especially p-tau217) can be used as "Core 1" biomarkers to establish a diagnosis of AD 4
• An abnormal Core 1 biomarker result is now considered sufficient to establish a diagnosis of AD and inform clinical decision making throughout the disease continuum 4

Future Directions

• Standardization of collection, processing, and storage procedures is needed before blood-based biomarkers can be effectively adopted in routine clinical settings 2, 1
• Practical guidelines covering study design, blood collection, processing, biobanking, biomarker measurement, and result reporting are being developed 2
• Combining blood biomarker detection with imaging markers may help improve the accuracy of AD diagnosis 3
• A centralized data-sharing platform could provide shared resources for validation of different blood-based biomarker assays 1