Abstract
BACKGROUND: With the introduction of disease-modifying treatments for Alzheimer's disease (AD), less invasive and widely accessible screening tests are urgently needed. We assessed eight blood-based biomarkers in a well-defined cohort of preclinical AD, including participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: Amyloid beta (Aβ) oligomerization tendency, Aβ42, Aβ40, Aβ42/Aβ40 ratio, phosphorylated tau (p-tau)181, p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (Nf-L) were assessed for distinguishing between SCD and MCI, for correlations, and for predicting Aβ positron emission tomography (PET) positivity. RESULTS: Plasma p-tau181, p-tau217, and GFAP levels were significantly higher in participants with MCI than in those with SCD (P >0.05) and in Aβ PET-positive versus Aβ PET-negative participants (P >0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were significantly lower in Aβ PET-positive than in Aβ PET-negative participants (P >0.001). Logistic regression analysis revealed that plasma Aβ42 and p-tau217 levels predicted Aβ PET positivity with an area under the ROC curve (AUC) of 0.930 (95% confidence interval [CI], 0.848-0.976) in the entire cohort, and p-tau217 alone predicted Aβ PET-positivity with an AUC of 0.887 (95% CI, 0.779-0.954) in the MCI subgroup. CONCLUSIONS: Plasma p-tau217 levels outperform plasma p-tau181 levels in predicting Aβ PET-positivity in participants with preclinical AD. Plasma GFAP levels, along with different p-tau isoforms (p-tau181 and p-tau217), effectively differentiate MCI from SCD. The predictive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clinical implementation, particularly with the introduction of disease-modifying therapies.