Blood-based biomarkers for detecting Alzheimer's disease pathology in cognitively impaired individuals within specialized care settings: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of diagnostic test accuracy studies
PubMed 41193403 · doi:10.1002/alz.70828
What was done
A systematic review and meta-analysis (MEDLINE, Embase, and Cochrane Library from January 2019 to November 2024) evaluated the diagnostic test accuracy of plasma biomarkers (p-tau217, %p-tau217, p-tau181, p-tau231, and Aβ42/Aβ40) compared to reference standard tests (CSF biomarkers, amyloid PET, or neuropathology). The population was individuals with objective cognitive impairment (mild cognitive impairment or dementia) in specialized care settings. Pooled sensitivity, specificity, likelihood ratios, and post-test probabilities were calculated. Risk of bias was evaluated via QUADAS-2, and evidence certainty via GRADE.
What was found
Across 49 observational studies evaluating 31 different blood-based biomarker tests with a single cut-point: - Pooled sensitivity ranged across tests from 49.3% (95% CI: 41.2% to 57.4%) to 91.4% (95% CI: 86.6% to 94.6%). - Pooled specificity ranged from 61.5% (95% CI: 45.6% to 75.3%) to 96.7% (95% CI: 87.8% to 99.2%). - Changes in post-test probability varied substantially by assay platform and baseline pre-test probability. - Certainty of evidence ranged from moderate to very low across tests.
Why it matters
This review establishes that diagnostic accuracy for Alzheimer's disease pathology is highly assay- and platform-specific in specialized clinical settings. It provides the empirical evidence base for the Alzheimer's Association clinical practice guideline on implementing blood tests.
Limits
Most included studies were judged at high risk of bias, particularly regarding patient selection, index test conduct, and reference standards. Accuracy estimates varied broadly across distinct platforms, precluding generalized assumptions about plasma biomarkers as a class. Findings are limited to specialized care settings and do not apply to primary care or asymptomatic screening.
Cited by
- context Blood-based p-tau217 testing performs as accurately as cerebrospinal fluid analysis and PET tau neuroimaging for Alzheimer's biomarker detection.