Blood Tests for Alzheimer's Disease: Current Status and Clinical Utility
Blood-based biomarker tests for Alzheimer's disease are now clinically available and represent a significant advancement in making AD diagnosis more accessible, though they vary in performance and are still evolving toward widespread clinical implementation. 1
Current Status of Blood-Based Biomarkers for AD
- Blood tests for Alzheimer's disease have seen significant progress in recent years, driven by technological advances that have improved analytical sensitivity and precision of measurement platforms 1
- Several blood-based biomarkers have demonstrated high potential for accurately detecting AD pathophysiology, including amyloid-beta (Aβ)40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau and glial fibrillary acidic protein 1
- A milestone was reached in 2020 when C2N Diagnostics introduced the first commercially available biomarker blood test detecting brain amyloid plaque 1
- Blood biomarkers are now widely used in AD research studies and clinical trials, with multiple tests becoming clinically available 1
Advantages of Blood-Based Biomarkers
- Blood tests are more acceptable to patients, more accessible, and can be rapidly scaled up compared to traditional biomarker testing methods like amyloid PET scans and cerebrospinal fluid (CSF) tests 1
- Blood-based biomarker tests have the potential to overcome challenges associated with PET and CSF testing, which are limited by high costs, invasiveness, and restricted availability 1
- Blood tests could be routinely performed in primary care and community-based settings, meeting scalability requirements that other testing methods cannot 1
- When widely available as initial diagnostic tools in primary care, blood-based biomarker tests will allow primary care providers to rapidly screen patients at risk for prodromal AD or mild AD dementia 1
Performance Standards for Clinical Use
- For use as a triaging test before subsequent confirmatory tests (like amyloid PET or CSF), a blood biomarker test should have a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75–85% in secondary care 1
- For use as a confirmatory test without follow-up tests, a blood biomarker test should have performance equivalent to CSF tests — a sensitivity and specificity of approximately 90% 1
- The most promising blood biomarker measures for amyloid status include the Aβ42/Aβ40 ratio and tau phosphorylated at different sites, including p-tau181, p-tau217, and p-tau231 1
- Assays of plasma p-tau217 or the ratio of p-tau217 to non-phosphorylated tau have shown particularly strong performance with AUCs of 0.92–0.98, similar to CSF tests for classifying amyloid PET status 1
Current Limitations and Challenges
- The lack of standardization in blood sample collection, processing, storage, analysis, and reporting affects the reproducibility of biomarker measurements 1
- Challenges remain with establishing blood-based biomarkers' technical performance, diagnostic accuracy, and prognostic value across diverse populations 1
- Blood tests currently require samples to be shipped to a centralized laboratory for analysis, though this limitation could be addressed as blood testing infrastructure becomes better established 1
- Different blood biomarker tests have widely varying performances for classification of amyloid status, even when designed to measure the same analyte 1
Clinical Implementation Path
- As anti-amyloid treatments become more widely available, biomarker testing to determine amyloid pathology is becoming an essential component of cognitive impairment assessment 1
- Blood biomarkers could serve as pre-screening measures to streamline identification of individuals for clinical trials or treatment 1
- Recent FDA-approved anti-amyloid drugs require confirmation of brain amyloidosis, making blood biomarkers potentially valuable proxies when amyloid PET and CSF assessments aren't feasible 1
- Educational campaigns for healthcare providers and the general public could raise awareness about the benefits of blood tests for Alzheimer's pathology, similar to routine testing in other areas like cholesterol screening 1
Future Directions
- Shared resources of neuroimaging, biofluid, digital, and other data types could facilitate development, validation, and generalizability of blood-based biomarkers 1
- Standardization of collection, processing, and storage procedures is needed before blood-based biomarkers can be effectively adopted in clinical settings 1
- Practical guidelines covering study design, blood collection, processing, biobanking, biomarker measurement, and result reporting are being developed to improve harmonization of sample handling and comparability across studies 1
- A centralized data-sharing platform could provide shared resources of blood samples with neuropathological validation of different blood-based biomarker assays for AD 1