To explore plasma phosphorylated tau (p-tau) 181 levels in Subjective Cognitive Decline and to investigate its role as a potential biomarker for Alzheimer’s Disease (AD) in Subjective Cognitive Decline (SCD).

One of the greatest challenges in AD is the discovery of new non-invasive, sensitive and specific biomarkers, which might be useful in the early stages such as SCD. Plasma p-tau181 is becoming increasingly notable in prodromal stages of AD, as a valuable marker for tauopathy, one of the core features of AD.

We included 27 SCD patients, who underwent clinical evaluation, neuropsychological assessment, Apolipoprotein E (APOE) genotyping, plasma p-tau181 analysis with SiMoA assay and cerebrospinal fluid (CSF) biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau).Patients were rated according to A/T(N) system and classified as carrier of AD pathology (AP+) when A+ was associated with either T+ or N+, or non-carriers (AP-) when they were classified as A- (regardless of T and N classification), or A+/T-/N-.

Plasma p-tau181 levels were correlated with CSF p-tau (ϱ=0.819, p<0.001) and also with age (ϱ=0.605, p=0.001), CSF Aβ1-42 (ϱ=-0.461, p=0.012), CSF Aβ1-42/1-40 (ϱ=-0.770, p<0.001) and CSF t-tau (ϱ=0.535, p=0.009).  A multivariate linear regression analysis showed that plasma p-tau181 were significantly associated only with CSF p-tau levels (p=0.027). When comparing AP+ and AP- subgroups, we found that plasma p-tau181 levels were significantly higher in the former group (2.85±0.53 vs 1.75±.66, p<0.001). A ROC curve analysis demonstrated that plasma p-tau181 was highly accurate for discriminating between AP+ and AP- SCD patients (AUC = 0.908).

Plasma p-tau181 levels strongly correlated with CSF p-tau. Plasma p-tau showed a high accuracy in differentiating SCD patients who were carriers from SCD patients who were non-carriers of AD pathology. Our preliminary results suggest that plasma p-tau181 might be a promising noninvasive biomarker of AD pathology which might be useful in preclinical stage of AD.