Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures

Abstract A combination of plasma phospho-tau (P-tau) and other accessible biomarkers may provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) who were consecutively recruited in the BioFINDER study (n=340). The results were validated in SCD/MCI participants in the ADNI study (n=543). Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and MRI (cortical thickness in AD-specific regions) were examined as predictors of progression to AD dementia primarily within 4 years. The accuracy was determined using the area under the ROC curve (AUC) from logistic regression models. Within 4 years, plasma P-tau217 predicted AD dementia accurately (AUC 0.83) in BioFINDER. A model of plasma P-tau217, memory, executive function, and APOE had higher accuracy (AUC 0.91, p<0.001). In ADNI, this model produced a similar AUC (0.90) using plasma P-tau181 instead of P-tau217. A cross-validated version of this model was implemented online for prediction of the individual probability of progressing to AD dementia. Within 2 and 6 years, parsimonious models performed similar in both cohorts (AUCs 0.90-0.91). Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy. The clinical prediction by memory clinic physicians had significantly lower accuracy than all models (4-year AUC 0.71). In summary, plasma P-tau in combination with brief cognitive tests and APOE genotyping may greatly improve the diagnostic prediction of AD dementia and facilitate recruitment for AD trials.