Introduction

Recently, plasma p-tau217 has shown to have a high accuracy in distinguishing individuals with and without amyloid-b (Ab) pathology which is important for trial selection. However, there is great heterogeneity in the prevalence of plasma p-tau217 positivity within clinical diagnostic groups, due to differences in diagnostic criteria, assays used and chosen cut-offs. Gaining insight into the prevalence is important for developing reliable and accurate protocols for using plasma p-tau217 as a diagnostic tool, in clinical trials, and for therapeutic purposes. Therefore, this meta-analysis aims to gain more insight into the prevalence of plasma p-tau217 positivity across the AD clinical spectrum.

 

Methods

A literature search was done in PubMed with the search terms: “Alzheimer’s disease”, “blood”, “p-tau217”, and synonyms. Non-research articles were removed before screening, such as reviews and commentaries. Articles were included if they focused on sporadic, late-onset AD and had prevalence data for plasma p-tau217 positivity. After inclusion, data regarding plasma p-tau217 prevalence, clinical diagnosis, cut-offs, assays used, and basic demographics were extracted. Random-effects meta-analysis to obtain a pooled estimate of the prevalence of p-tau217 positivity per clinical group was performed in R.

 

Results

The literature search identified 305 articles, of which 21 had prevalence data per clinical group, with a total of 9,181 persons (mean age 64.04 years, 61.7% female). In these, the Lumipulse platform was used in 3 articles, a Simoa in 14, and a Meso Scale Discovery assay in 4. Preliminary results show that the prevalence of p-tau217 positivity was 20% (95% CI: 15%–26%, N_articles=12, I² = 87.9%; figure 1) in cognitively unimpaired persons, 50% (95% CI: 41%-58%, N_articles=13, I² = 88.5%; figure 2) in participants with MCI, and 83% (95% CI: 74%-89%, N_articles=15, I² = 92.3%; figure 3) in persons with clinical AD dementia.

 

Conclusion

These preliminary results show that the prevalence of plasma p-tau217 positivity differs per clinical group and that these are comparable to previously established PET- and CSF-based estimates of amyloid positivity. In addition, the high I² indicates great heterogeneity. Further analyses and meta-regression will provide more insight into sources of this heterogeneity, aiding in the development of tools for identifying early AD, facilitating timely intervention.