Cerebrospinal fluid tau and β-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment

Context: Cerebrospinal fluid tau protein and β-amyloid 42 (Aβ42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI). Objective: To investigate the potential of cerebrospinal fluid tau and Aβ42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months. Design: An 18-month prospective study. Setting: Clinical follow-up study of community-residing subjects with MCI. Main Outcome Measures: Cerebrospinal fluid tau and Aβ42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis. Results: Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P=.002) and subjects with progressive MCI (P=.003) compared with subjects who had stable MCI. Cerebrospinal fluid Aβ42 levels were significantly lower in patients who progressed to probable AD (P=.007) and those with progressive MCI (P=.04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P=.02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P=.03). Conclusion: Our results indicate that altered tau and Aβ42 concentrations maybe detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.