Diagnostic Performance of Eight Blood-based Biomarkers in a Well-characterized Korean Cohort of Preclinical Alzheimer’s Disease
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: With the introduction of disease-modifying treatments for Alzheimer’s dis- ease (AD), less invasive and widely accessible screening tests are urgently needed. We as- sessed 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 neurofil- ament 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 partici- pants with MCI than in those with SCD (P <0.05) and in Aβ PET-positive versus Aβ PET-neg- ative participants (P <0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were sig- nificantly 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 posi- tivity 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 predic- tive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clini- cal implementation, particularly with the introduction of disease-modifying therapies.
Abstract
Background: With the introduction of disease-modifying treatments for Alzheimer’s dis- ease (AD), less invasive and widely accessible screening tests are urgently needed. We as- sessed 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 neurofil- ament 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 partici- pants with MCI than in those with SCD (P <0.05) and in Aβ PET-positive versus Aβ PET-neg- ative participants (P <0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were sig- nificantly 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 posi- tivity 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 predic- tive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clini- cal implementation, particularly with the introduction of disease-modifying therapies.