Expression differences and diagnostic efficacy of core plasma biomarkers in Alzheimer’s disease, cerebral small vessel disease and healthy adults

Abstract

Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) are the two leading causes of cognitive impairment in the elderly, with overlapping clinical manifestations. This study aimed to explore the expression differences of plasma Aβ1-42, Aβ1-40, Aβ1-42/Aβ1-40, p-Tau181, p-Tau217, NfL and GFAP among patients with AD, CSVD and healthy populations, and to evaluate the diagnostic value of these biomarkers for AD as well as the differential diagnostic efficacy between AD and CSVD. A total of 120 participants were enrolled and divided into AD group, CSVD group and healthy control group, with 40 cases in each group. Plasma biomarkers were detected by chemiluminescence immunoassay, and cognitive function and neuroimaging examinations were completed simultaneously. The differences of biomarker levels among the three groups were compared. Spearman correlation analysis was used to analyze the correlation between each biomarker and MMSE score, and ROC curve was adopted to evaluate the diagnostic and differential diagnostic efficacy of single biomarker. Plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were significantly decreased, while p-Tau181 and p-Tau217 were markedly elevated in the AD group. The GFAP level in the CSVD group was specifically and significantly higher than that in the AD group and healthy control group. NfL was significantly increased in both disease groups. p-Tau217 exhibited optimal efficacy in distinguishing AD from healthy controls (AUC = 0.894) and differentiating AD from CSVD (AUC = 0.877). GFAP showed excellent diagnostic value in distinguishing CSVD from healthy controls (AUC = 0.881). All biomarkers were significantly correlated with MMSE scores. Among patients with isolated AD or isolated CSVD, plasma p-Tau217 is the optimal specific biomarker for the diagnosis of AD and differentiation between AD and cerebral small vessel disease. GFAP acts as a key indicator for identifying CSVD. These findings should be interpreted cautiously for patients with AD-CSVD co-pathology. Combined detection of multiple plasma biomarkers provides an important clinical basis for non-invasive early screening and etiological classification of cognitive impairment in patients with pathologically isolated cognitive disorders.