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

• Published in: Molecular psychiatry Vol. 9; no. 7; pp. 705 - 710
• Main Authors: Hampel, H, Teipel, S J, Fuchsberger, T, Andreasen, N, Wiltfang, J, Otto, M, Shen, Y, Dodel, R, Du, Y, Farlow, M, Möller, H-J, Blennow, K, Buerger, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2004; Nature Publishing Group
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E; Apolipoprotein E4; Apolipoproteins E - genetics; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Biomarkers; Cerebrospinal fluid; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - diagnosis; Cognition Disorders - genetics; Cognitive ability; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neurodegenerative diseases; Neurology; Neurosciences; original-research-article; Patients; Peptide Fragments - cerebrospinal fluid; Pharmacotherapy; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Proteins; Psychiatry; Sensitivity and Specificity; Severity of Illness Index; Tau protein; tau Proteins - cerebrospinal fluid; beta-amyloid; early diagnosis; mild cognitive impairment (MCI); prediction; Alzheimer's disease (AD); tau; cerebro-spinal fluid (CSF); biomarker; prognosis; conversion; Human; Nervous system diseases; Tau protein; Alzheimer disease; β Amyloid protein; Predictor; Central nervous system disease; Degenerative disease; mild cognitive impairment; Cerebrospinal fluid; Cerebral disorder
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001473

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 -amyloid 1–42 (A β 1–42 ) 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 A β 1–42 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 A β 1–42 and CSF tau. The levels of CSF tau were increased, whereas levels of A β 1–42 were decreased in MCI subjects. A β 1–42 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 A β 1–42 , but not other predictor variables (tau protein, gender, age, apolipoprotein E ɛ 4 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 A β 1–42 may be useful biomarkers in the early identification of AD in MCI subjects.