SELECTED BLOOD-BASED BIOMARKERS IN ALZHEIMER'S DISEASE: CLINICAL APPLICATIONS, DIAGNOSTIC UTILITY, AND IMPLEMENTATION CHALLENGES
TL;DR
Plasma biomarkers offer a transformative, non-invasive approach to early AD diagnosis and primary care triage, reducing reliance on CSF and PET scans and overcoming demographic and methodological limitations is essential for their widespread clinical adoption.
Abstract
Background: Alzheimer’s disease (AD) poses major public health challenges. Traditional CSF and PET diagnostics are invasive, expensive, and limited in routine practice, driving the need for accessible plasma biomarkers. Objectives: To evaluate the diagnostic and prognostic utility of key plasma biomarkers (plasma Aβ42/Aβ40 ratio, p-tau species, NfL, t-tau, GFAP, sTREM2) and identify limitations to their clinical implementation. Methods: A structured literature search was conducted in the PubMed database for English-language clinical studies and review articles published between October 2007 and June 2026. Keywords and MeSH terms included "Alzheimer’s disease", "blood-based biomarkers", "immunoprecipitation-mass spectrometry (IP-MS)", and "mild cognitive impairment". Studies focusing on adult clinical biomarkers underwent a narrative synthesis. Results: Plasma Aβ42/Aβ40 and p-tau species (p-tau181, p-tau231, p-tau217) reliably detect early amyloid pathology and differentiate AD from other dementias. NfL, GFAP, and sTREM2 track axonal damage, astrogliosis, and microglial activity, facilitating disease monitoring and therapeutic response assessment. However, clinical translation is constrained by demographic variations, somatic comorbidities, and a lack of standardized multi-marker reference ranges. Conclusions: Plasma biomarkers offer a transformative, non-invasive approach to early AD diagnosis and primary care triage, reducing reliance on CSF and PET scans. Overcoming demographic and methodological limitations is essential for their widespread clinical adoption.