Background High-performance blood tests may improve diagnostic accuracy and support personalized treatment for Alzheimer's disease (AD), but validation at the time of initial clinical diagnosis remains limited. Objective To assess whether plasma biomarkers can aid diagnostic decision-making at first clinical assessment, particularly as tools to triage patients for confirmatory testing in routine practice. Methods We analyzed 241 cognitively normal (CN) controls, 211 patients with mild cognitive impairment (MCI), and 59 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. Plasma aliquots underwent analysis with the C2N Diagnostics PrecivityAD2 ® and Roche Diagnostics Elecsys ® assays. Results The AD group showed a lower Aβ 42 /Aβ 40 ratio than the CN group (p < 0.01) and a mild decrease compared to the MCI group (p < 0.05). The AD group had significant increases in p-tau181, p-tau217, and %p-tau217 (p < 0.001) versus both MCI and CN groups. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were also significantly elevated in AD. The MCI and CN groups only differed in p-tau217 and %p-tau217 (p < 0.05). The AD versus CN AUCs for p-tau181, p-tau217, and %p-tau217 were 0.84, 0.87, and 0.87; for AD versus MCI, they were 0.79, 0.80, and 0.81. The p-tau181, p-tau217, and %p-tau217 showed a moderate correlation with the Alzheimer's Disease Assessment Scale-cognitive subscale. %p-tau217 demonstrated a strong correlation with the p-tau181/Aβ 42 ratio in CSF (R = 0.72, p < 0.001). Conclusions In the setting of first-presentation diagnosis of clinically defined MCI and AD, p-tau217, and %p-tau217 outperformed other plasma biomarkers and may help triage patients for further confirmatory evaluation.
Qiu et al. (Sun,) studied this question.