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Plasmin system of Alzheimer’s disease patients: CSF analysis

  • Dementias - Original Article
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Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by the extracellular deposit of Amyloid beta (Aβ), mainly of the Amyloid beta1–42 (Aβ1–42) 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 Aβ1–42 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 Aβ1–42, 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.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid beta

1–42 :

Amyloid beta1–42

t-PA:

Tissue plasminogen activator

PAI-1:

Plasminogen activator inhibitor

CSF:

Cerebrospinal fluid

APP:

Amyloid precursor protein

u-PA:

Urokinase plasminogen activator

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Acknowledgments

We thank Bender MedSystems for a generous gift of t-PA and PAI-1 ELISA kit.

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The authors have no conflict of interest.

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Correspondence to Alessandro Martorana.

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Martorana, A., Sancesario, G.M., Esposito, Z. et al. Plasmin system of Alzheimer’s disease patients: CSF analysis. J Neural Transm 119, 763–769 (2012). https://doi.org/10.1007/s00702-012-0778-y

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  • DOI: https://doi.org/10.1007/s00702-012-0778-y

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