Cerebrospinal fluid markers for prediction of Alzheimer's disease

A major diagnostic challenge when people seek advice for cognitive dysfunction is to differentiate between mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). We show that a combination of three cerebrospinal fluid biochemical markers, total-tau, phospho-tau and beta-amyloid(1-42), can detect incipient AD among patients fulfilling the criteria for MCI with a sensitivity of 68% (95% CI 45-86%) and a specificity of 97% (95% CI 83-100%). The usefulness of these markers is further emphasized by the finding of a positive predictive value of 94% and a negative predictive value of 81%.

[1]  H. Arai,et al.  CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects , 2002, Neurology.

[2]  K. Blennow,et al.  Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization , 2000, Neuroscience Letters.

[3]  Kaj Blennow,et al.  Cerebrospinal fluid levels of total‐tau, phospho‐tau and Aβ42 predicts development of Alzheimer's disease in patients with mild cognitive impairment , 2003 .

[4]  K. Blennow,et al.  Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment , 1999, Neuroscience Letters.

[5]  P. Deyn,et al.  Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF , 1999, Neurology.

[6]  K. Blennow,et al.  Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. , 2001, Archives of neurology.

[7]  Nobuyuki Okamura,et al.  CSF Phosphorylated Tau Protein and Mild Cognitive Impairment: A Prospective Study , 2000, Experimental Neurology.

[8]  K. Blennow,et al.  Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. , 1999, Archives of neurology.

[9]  K. Schulz,et al.  Uses and abuses of screening tests , 2002, The Lancet.

[10]  H. Arai Elevated cerebrospinal fluid tau protein level as a predictor of dementia in memory-impaired individuals , 1997 .

[11]  H. Vanderstichele,et al.  Cerebrospinal beta-amyloid (1–42) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline , 2000, Neuroscience Letters.

[12]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[13]  K. Blennow,et al.  Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values. , 2001, Clinical chemistry.

[14]  J. Kaye,et al.  High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. , 1998, Archives of neurology.

[15]  A. Kurz,et al.  Tau Protein in Cerebrospinal Fluid Is Significantly Increased at the Earliest Clinical Stage of Alzheimer Disease , 1998, Alzheimer disease and associated disorders.

[16]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.

[17]  D. Galasko,et al.  Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease , 1997, Neurology.

[18]  A. Kurz,et al.  Cerebrospinal protein tau is elevated in early Alzheimer's disease , 1996, Neuroscience Letters.

[19]  D. Schaid,et al.  Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. , 1995, JAMA.