CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases.

The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD) calls for discovery and validation of biomarkers. Increased cerebrospinal fluid (CSF) tau and decreased amyloid (A) beta42 have been validated as biomarkers of AD. In contrast, there is no validated CSF biomarker for PD. We validated our proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects, 48 patients with probable AD, and 40 patients with probable PD. An optimal 8-member MAP agreed with expert diagnosis for 90 control subjects (95%), 36 patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP consisted of the following (in decreasing order of contribution): tau, brain-derived neurotrophic factor, interleukin 8, Abeta42, beta2-microglobulin, vitamin D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale validation of a proteomic-discovered MAP suggests a panel of 8 CSF proteins that are highly effective at identifying PD and moderately effective at identifying AD.

[1]  Norman Relkin,et al.  Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease , 2007, Annals of neurology.

[2]  D. Galasko.  Biomarkers for Alzheimer's disease--clinical needs and application. , 2006, Journal of Alzheimer's disease : JAD.

[3]  R. Faber,et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. , 1999, Neurology.

[4]  W. Poewe,et al.  Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson's disease , 2004, Movement disorders : official journal of the Movement Disorder Society.

[5]  Gunhild Waldemar,et al.  Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment. , 2007, Archives of neurology.

[6]  J. Kaye,et al.  Safety and Acceptability of the Research Lumbar Puncture , 2005, Alzheimer disease and associated disorders.

[7]  M. Freedman,et al.  Frontotemporal lobar degeneration , 1998, Neurology.

[8]  Jing Zhang,et al.  Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease. , 2005, Journal of Alzheimer's disease : JAD.

[9]  Ramón Díaz-Uriarte,et al.  Gene selection and classification of microarray data using random forest , 2006, BMC Bioinformatics.

[10]  Yan Liu,et al.  Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. , 2006, Journal of Alzheimer's disease : JAD.

[11]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[12]  T. Beach,et al.  Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects , 2006, Neurological research.

[13]  Kaj Blennow,et al.  Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients , 2002, Neuroreport.

[14]  J. Morris,et al.  Clinical Dementia Rating: A Reliable and Valid Diagnostic and Staging Measure for Dementia of the Alzheimer Type , 1997, International Psychogeriatrics.

[15]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[16]  Kaj Blennow,et al.  Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. , 2003, Brain research. Molecular brain research.

[17]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .

[18]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[19]  S. Gilman,et al.  Diagnostic criteria for Parkinson disease. , 1999, Archives of neurology.