title: Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease.
abstract: Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
authors.affiliation: Department of Neuroscience and Physiology, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Mölndal, Sweden. Electronic address: Kaj.Blennow@neuro.gu.se.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Institute for Memory and Alzheimer's Disease, Institute of Neurology, Pitié-Salpêtrière Hospital Group, Pierre and Marie Curie University, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY, USA; Centre for Brain Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.affiliation: Institute for Memory and Alzheimer's Disease, Institute of Neurology, Pitié-Salpêtrière Hospital Group, Pierre and Marie Curie University, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D007118:Immunoassay / Q000592:standards; D059906:Neuroimaging; D015203:Reproducibility of Results; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
keywords: Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Mild cognitive impairment; Tau protein; β-Amyloid