CSF phosphorylated tau in the diagnosis and prognosis of mild cognitive impairment and Alzheimer's disease: a meta-analysis of 51 studies

Objective: To evaluate the accuracy and clinical utility of phosphorylated tau (p-tau) for the diagnosis and prognosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A meta-analysis was performed of 19 robust studies that compared AD with healthy individuals (n = 2300), 18 that compared AD with non-AD dementias (n = 1892), eight that compared MCI with healthy subjects (n = 447) and six in those with MCI who did and did not progress to dementia (n = 388). Results: On the basis of levels of p-tau in CSF, AD could be discriminated from those without cognitive impairment with a sensitivity (Se) of 77.6%, a specificity (Sp) of 87.9%, a positive predictive value (PPV) of 90.3% and a negative predictive value (NPV) of 73.0%. The clinical utility of the test was rated as "good''. CSF levels of p-tau separated AD from other dementias with an Se of 71.6% and an Sp 77.8% but here the clinical utility was satisfactory to poor. Regarding MCI, p-tau contributed to the separation of MCI from healthy individuals with an Se of 79.6% and an Sp 83.9% (PPV 85.9%, NPV 76.9%). Here the clinical utility was rated as "satisfactory''. P-tau was modestly successful in predicting progression to dementia in MCI (Se 81.1%, Sp 65.3%, PPV 63.0%, NPV 83.0%), showing higher predictive value for absence of progression rather than conversion to AD. Conclusions: CSF p-tau is a good diagnostic biomarker of probable AD, a satisfactory diagnostic biomarker of MCI, a satisfactory prognostic biomarker for progression of MCI but was less adequate in separating AD from other dementias.