Phosphorylated tau predicts rate of cognitive decline in MCI subjects: A comparative CSF study

A significant increase in hyperphosphorylated tau proteins (P-tau) in CSF has been shown in Alzheimer disease (AD), suggesting potential utility as biologic markers of AD.¹ Different subtypes of P-tau proteins perform differently in the discrimination of primary dementia disorders from AD.² Recently, we have shown that tau phosphorylated at threonine 231 (P-tau_231P) correlates with cognitive decline in subjects with mild cognitive impairment (MCI),³ a group at risk for AD.⁴ Here, we examined in an exploratory study whether different P-tau epitopes differ in their accuracy to predict cognitive deterioration within subjects with MCI. Therefore, previously published results on P-tau_231P are again presented briefly for comparison. Moreover, we wished to know whether a combination of different P-tau epitopes is superior to a single P-tau marker for the prediction of cognitive decline.

Three P-tau subtypes were measured at baseline in 59 patients with MCI.⁴ Clinical follow-up was performed in all patients (mean interval 12.27 months, range 6 to 42 months). The mean (SD) age of the MCI patients (28 female) was 72.56 (7.6) years with a mean Mini-Mental State Examination (MMSE) score of 28.0 (1.9). There were 23 healthy control subjects (HC; 14 female; age 60.0 ± 10.1 years; MMSE 29.2 ± 0.7 points). Study subjects were recruited at two centers (Department of Psychiatry, Ludwig Maximilian University, Munich, Germany, and …