Role of Blood P-Tau Isoforms (181, 217, 231) in Predicting Conversion from MCI to Dementia Due to Alzheimer's Disease: A Review and Meta-Analysis

Blood-based biomarkers are minimally invasive tools to detect the pathological changes of Alzheimer's Disease (AD). This meta-analysis aims to investigate the use of blood-derived p-tau isoforms (181, 217, 231) to predict conversion from mild cognitive impairment (MCI) to AD dementia (ADD). Studies involving MCI patients with data on blood p-tau isoforms at baseline and clinical diagnosis at follow-up (≥1 year) were included. Twelve studies on p-tau 181 (4340 MCI, conversion rate 20.6%), four on p-tau 217 (913 MCI, conversion rate 33.4%), and one on p-tau 231 (135 MCI, conversion rate 33%) were included. For p-tau 181, the pooled area under the receiver operating characteristic curve (AUC) was 0.73 (95% CI = 0.68-0.78), and for p-tau 217 was 0.85 (95% CI = 0.75-0.91). Plasma levels of p-tau 181 had good discriminatory power to identify MCI patients who will convert to ADD. Although only four studies on p-tau 217 have been included in the meta-analysis, in the last year the predictive power of p-tau 217 is emerging as superior to that of other isoforms. However, given the high heterogeneity detected in the p-tau 217 studies included in this meta-analysis, additional supportive evidence is needed. Insufficient results were available for p-tau 231. These findings support the prognostic utility of p-tau 181 and p-tau 217 measured in blood to predict progression to ADD in MCI and encourage its future implementation in clinical practice.