Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.
Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-beta immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-beta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, SE-431 80 Mölndal, Sweden. kaj.blennow@neuro.gu.se
Kaj
K
Blennow
Harald
H
Hampel
Michael
M
Weiner
Henrik
H
Zetterberg
D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology; D006801:Humans; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins