title: Modeling of pathological traits in Alzheimer's disease based on systemic extracellular signaling proteome.
abstract: The study of chronic brain diseases including Alzheimer's disease in patients is typically limited to brain imaging or psychometric testing. Given the epidemic rise and insufficient knowledge about pathological pathways in sporadic Alzheimer's disease, new tools are required to identify the molecular changes underlying this disease. We hypothesize that levels of specific secreted cellular signaling proteins in cerebrospinal fluid or plasma correlate with pathological changes in the Alzheimer's disease brain and can thus be used to discover signaling pathways altered in the disease. Here we measured 91 proteins of this subset of the cellular communication proteome in plasma or cerebrospinal fluid in patients with Alzheimer's disease and cognitively normal controls to mathematically model disease-specific molecular traits. We found small numbers of signaling proteins that were able to model key pathological markers of Alzheimer's disease, including levels of cerebrospinal fluid β-amyloid and tau, and classify disease in independent samples. Several of these factors had previously been implicated in Alzheimer's disease supporting the validity of our approach. Our study also points to proteins which were previously unknown to be associated with Alzheimer's disease thereby implicating novel signaling pathways in this disorder.
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5235, USA. markus.britschgi@roche.com
authors: Markus
authors: M
authors: Britschgi
authors: Kaspar
authors: K
authors: Rufibach
authors: Sarah L Bauer
authors: SL
authors: Huang
authors: Christopher M
authors: CM
authors: Clark
authors: Jeffrey A
authors: JA
authors: Kaye
authors: Ge
authors: G
authors: Li
authors: Elaine R
authors: ER
authors: Peskind
authors: Joseph F
authors: JF
authors: Quinn
authors: Douglas R
authors: DR
authors: Galasko
authors: Tony
authors: T
authors: Wyss-Coray
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D001798:Blood Proteins / Q000032:analysis*; D002450:Cell Communication; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D059906:Neuroimaging; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D020543:Proteome / Q000032:analysis*; D015398:Signal Transduction; D016875:tau Proteins / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D001798:Blood Proteins; D002556:Cerebrospinal Fluid Proteins; D010446:Peptide Fragments; D020543:Proteome; D016875:tau Proteins