Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease

Background Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the association with cognitive domains along the spectrum of cognitive performance deterioration have seldom been reported. Methods We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis of AD, amnestic mild cognitive impairment, and normal cognition (NC). Each participant was administered the neuropsychological tests assessing the global and domain-specific cognition. Plasma Aβ 1-40 , Aβ 1-42 , Aβ 1-42 /Aβ 1-40 , total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the Single molecule array platform. Results Along with plasma Aβ 1-40 , Aβ 1-42 , Aβ 1-42 /Aβ 1-40 , t-tau, and NfL, p-tau181 significantly increased across the groups with the incremental CDR scores from NC (CDR = 0) to severe AD (CDR = 3). Compared with other biomarkers, p-tau181 had a stronger correlation with Global cognition ( r = −0.494, P < 0.001), Memory ( r = −0.417, P < 0.001), Attention ( r = −0.388, P < 0.001), Visuospatial function ( r = −0.328, P < 0.001), and Language ( r = −0.123, P = 0.014). Among AD participants with CDR ≥ 1, higher p-tau181 was correlated with worse Global cognition ( r = −0.295, P < 0.001), Memory ( r = −0.172, P = 0.045), and Attention ( r = −0.184, P = 0.031). Conclusions Plasma p-tau181 had a stronger correlation with cognitive domains than other biomarkers, especially in late-stage AD. It could reflect the AD pathology in vivo and may be a promising blood-based biomarker in clinical settings.