title: Biomarker discovery for Alzheimer's disease, frontotemporal lobar degeneration, and Parkinson's disease.
abstract: Ante-mortem diagnosis of neurodegenerative disorders based on clinical features alone is associated with variable sensitivity and specificity, and biomarkers can potentially improve the accuracy of clinical diagnosis. In patients suspected of having Alzheimer's disease (AD), alterations in cerebrospinal fluid (CSF) biomarkers that reflect the neuropathologic changes of AD strongly support the diagnosis, although there is a trade-off between sensitivity and specificity due to similar changes in cognitively healthy subjects. Here, we review the current approaches in using CSF AD biomarkers (total tau, p-tau(181), and Abeta42) to predict the presence of AD pathology, and our recent work using multi-analyte profiling to derive novel biomarkers for biofluid-based AD diagnosis. We also review our use of the multi-analyte profiling strategy to identify novel biomarkers that can distinguish between subtypes of frontotemporal lobar degeneration, and those at risk of developing cognitive impairment in Parkinson's disease. Multi-analyte profiling is a powerful tool for biomarker discovery in complex neurodegenerative disorders, and analytes associated with one or more diseases may shed light on relevant biological pathways and potential targets for intervention.
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Hu
authors.forename: Alice
authors.initials: A
authors.lastname: Chen-Plotkin
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Leo
authors.initials: L
authors.lastname: McCluskey
authors.forename: Lauren
authors.initials: L
authors.lastname: Elman
authors.forename: Jason
authors.initials: J
authors.lastname: Karlawish
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001681:Biological Assay / Q000379:methods; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid*; D006801:Humans; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins