title: Plasmin system of Alzheimer's disease patients: CSF analysis.
abstract: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by the extracellular deposit of Amyloid beta (Aβ), mainly of the Amyloid beta(1-42) (Aβ(1-42)) peptide in the hippocampus and neocortex leading to progressive cognitive decline and dementia. The possible imbalance between the Aβ production/degradation process was suggested to contribute to the pathogenesis of AD. Among others, the serine protease plasmin has shown to be involved in Aβ(1-42) clearance, a hypothesis strengthened by neuropathological studies on AD brains. To explore whether there is a change in plasmin system in CSF of AD patients, we analyzed CSF samples from AD and age-matched controls, looking at plasminogen, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) protein levels and t-PA and urokinase plasminogen activator (u-PA) enzymatic activities. We also measured Aβ(1-42), total-tau and phospho-tau (181) CSF levels and sought for a possible relationship between them and plasmin system values. Our findings showed that t-PA, plasminogen and PAI-1 levels, as t-PA enzymatic activity, remained unchanged in AD with respect to controls; u-PA activity was not detected. We conclude that CSF analysis of plasminogen system does not reflect changes observed post-mortem. Unfortunately, the CSF detection of plasmin system could not be a useful biomarker for either AD diagnosis or disease progression. However, these findings do not exclude the possible involvement of the plasmin system in AD.
authors.affiliation: Department of Neuroscience, University of Rome Tor Vergata, 1 Montpellier Street, 00133, Rome, Italy. martorana@med.uniroma2.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Sancesario
authors.forename: Zaira
authors.initials: Z
authors.lastname: Esposito
authors.forename: Marzia
authors.initials: M
authors.lastname: Nuccetelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorge
authors.forename: Amanda
authors.initials: A
authors.lastname: Formosa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dinallo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005341:Fibrinolysin / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D010958:Plasminogen / Q000134:cerebrospinal fluid*; D017395:Plasminogen Activator Inhibitor 1 / Q000134:cerebrospinal fluid*; D010959:Tissue Plasminogen Activator / Q000134:cerebrospinal fluid*; D014568:Urokinase-Type Plasminogen Activator / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator