Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment

Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) β-amyloid1–42 (Aβ1–42) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Aβ1–42 and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Aβ1–42 and CSF tau. The levels of CSF tau were increased, whereas levels of Aβ1–42 were decreased in MCI subjects. Aβ1–42 predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Aβ1–42, but not other predictor variables (tau protein, gender, age, apolipoprotein E ɛ4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (P<0.05). Our findings support the notion that CSF tau and Aβ1–42 may be useful biomarkers in the early identification of AD in MCI subjects.