Plasma p-tau217, p-tau181 and Aβ42/40 for Alzheimer’s disease diagnosis: ROC accuracy and 18F-florbetapir amyloid PET-CT concordance

Early diagnosis of Alzheimer's disease (AD) presents significant challenges. This study assessed the diagnostic utility of seven plasma biomarkers and PET-CT imaging in cognitively healthy individuals (HC), those with mild cognitive impairment (MCI), and AD patients. Seventy participants (20 with MCI, 35 with AD, and 15 HC) underwent plasma testing for amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), the Aβ42/Aβ40 ratio, phosphorylated tau 181 (p-tau181), p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), along with cognitive assessments using the Mini-Mental State Examination (MMSE). Statistical comparisons among groups were performed, and receiver operating characteristic (ROC) curves were utilized to evaluate diagnostic accuracy. Spearman's correlation coefficient was applied to examine the relationships between biomarkers and MMSE scores. Additionally, 18 patients, including 14 with AD and 4 with MCI, underwent 18F-Florbetapir (18F-AV45) PET-CT amyloid imaging. The consistency between plasma biomarkers and PET-CT in detecting amyloid pathology was evaluated using Cohen's Kappa. Plasma Aβ42 levels and the Aβ42/Aβ40 ratio were significantly lower in AD patients compared to those with MCI and HC (p<0.05), while levels of p-tau181, p-tau217, NfL, and GFAP were significantly elevated (p<0.05). Aβ42 and the Aβ42/Aβ40 ratio exhibited positive correlations with MMSE scores (p<0.01), whereas p-tau181, p-tau217, GFAP, and NfL demonstrated negative correlations (p<0.001). The plasma Aβ42/Aβ40 ratio, p-tau181, and p-tau217 levels showed significant concordance with 18F-AV45 PET-CT results for detecting amyloid deposition (p<0.05). A reduced plasma Aβ42/Aβ40 ratio, along with increased p-tau181 and p-tau217 levels, is significantly associated with a clinical diagnosis of AD, cognitive decline (as indicated by lower MMSE scores), and positive amyloid deposition on PET-CT. These three core biomarkers, when combined with GFAP and NfL, may enhance diagnostic accuracy for AD in cross-sectional assessments, particularly when integrated with imaging and cognitive evaluations.