Plasmin system of Alzheimer's disease patients: CSF analysis.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by the extracellular deposit of Amyloid beta (Aß), mainly of the Amyloid beta(1-42) (Aß(1-42)) peptide in the hippocampus and neocortex leading to progressive cognitive decline and dementia. The possible imbalance between the Aß production/degradation process was suggested to contribute to the pathogenesis of AD. Among others, the serine protease plasmin has shown to be involved in Aß(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 Aß(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.

[In vitro studies to elucidate the fibrinolytic activity in cerebrospinal fluid altered by inflammation and hemorrhage and having pathologic protein values]. / In-vitro Versuche zur Klärung der fibrinolytischen Aktivität in entzündlich veränderten und blutigen Liquores mit pathologischen Proteinwerten.

Using selectively immunological methods, it was possible, through FSP determination, for plasmin activities and plasminogen concentrations to be occasionally and exclusively detected in inflammatorily altered liquores and in bloody liquores, respectively. Thus, bloody cerebrospinal fluid, in contrast with inflammatorily altered liquor, usually shows free fibrinolytic activity, so that antifibrinolytic therapy of intracranial aneurysmal hemorrhage is pathophysiologically justifiable.

[In-vitro experiments on the clarification of the fibrinolytic activity in normal cerebrospinal fluid]. / In-vitro-Versuche zur Klärung der fibrinolytischen Aktivität im Normalliquor.

A direct and indirect detection of plasmin in native CSF was not possible by the thrombelastographic and hot fibrin agar plate method and by electroimmunodiffusion analysis using Laurell's method of fibrin degradation product determination, respectively. The same method was used to determine concentrations of plasminogen and fibrinogen. The CSF, which were retrospectively judged to be normal, neither showed plasmin activity nor exhibited plasminogen and fibrinogen concentrations. Therefore, the liqour possesses only a plasminogen activator protein and does not represent a fibrinolytically active CSF.