Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 7:14:871214.
doi: 10.3389/fnagi.2022.871214. eCollection 2022.

Plasma Levels of Tissue-Type Plasminogen Activator (tPA) in Normal Aging and Alzheimer's Disease: Links With Cognition, Brain Structure, Brain Function and Amyloid Burden

Clémence Tomadesso  1   2 , Sara Martinez de Lizarrondo  1 , Carine Ali  1 , Brigitte Landeau  1 , Florence Mézenge  1 , Audrey Perrotin  1 , Vincent de La Sayette  1 , Denis Vivien  1   2 , Gaël Chételat  1
Affiliations

Plasma Levels of Tissue-Type Plasminogen Activator (tPA) in Normal Aging and Alzheimer's Disease: Links With Cognition, Brain Structure, Brain Function and Amyloid Burden

Clémence Tomadesso et al. Front Aging Neurosci. .

Abstract

Tissue-type plasminogen activator (tPA) is a protease known for its fibrinolytic action but is also involved in physiological and pathophysiological aging processes; including amyloid elimination and synaptic plasticity. The aim of the study was to investigate the role of tPA in cognitive and brain aging. Therefore, we assessed the links between tPA plasma concentration and cognition, structural MRI, FDG-PET and Flobetapir-PET neuroimaging in 155 cognitively unimpaired adults (CUA, aged 20-85 years old) and 32 patients with Alzheimer's disease (ALZ). A positive correlation was found between tPA and age in CUA (p < 0.001), with males showing higher tPA than females (p = 0.05). No significant difference was found between ALZ patients and cognitively unimpaired elders (CUE). Plasma tPA in CUA negatively correlated with global brain volume. No correlation was found with brain FDG metabolism or amyloid deposition. Age-related tPA changes were associated to changes in blood pressure, glycemia and body mass index. Within the ALZ patients, tPA didn't correlate with any cognitive or neuroimaging measures, but only with physiological measures. Altogether our study suggests that increased tPA plasma concentration with age is related to neuronal alterations and cardiovascular risk factors.

Keywords: Alzheimer's disease; FDG-PET; Flobetapir-PET; MRI; biological markers; cognition; normal aging; tissue plasminogen activator.

PubMed Disclaimer

Conflict of interest statement

AP currently works for Life Molecular Imaging GmbH, Berlin, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlation between age and tPA concentration within the CUA (A) and comparison of tPA plasma concentration between CUE and ALZ patients groups (B). tPA, tissue Plasminogen Activator; CUA, Cognitively Unimpaired Adults; ns, no statistically significant difference.
Figure 2
Figure 2
Voxelwise correlations between tPA plasma concentration and gray matter volume (negative correlation) within the CUA group with age and sex as covariates. tPA, tissue Plasminogen Activator; CUA, Cognitively Unimpaired Adults; MRI, Magnetic Resonance Imaging; FDG, 18F-fluorodeoxyglucose; PET, Positron Emission Tomography.
See this image and copyright information in PMC

References

    1. Akhter H., Huang W.-T., van Groen T., Kuo H.-C., Miyata T., Liu R.-M. (2018). A small molecule inhibitor of plasminogen activator inhibitor-1 reduces brain amyloid-β load and improves memory in an animal model of Alzheimer's Disease. J. Alzheimer's Dis. 64, 447–457. 10.3233/JAD-180241 - DOI - PubMed
    1. Asselbergs F. W., Williams S. M., Hebert P. R., Coffey C. S., Hillege H. L., Navis G., et al. (2007). Gender-specific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits. J. Thromb. Haemost. 5, 313–320. 10.1111/j.1538-7836.2007.02311.x - DOI - PubMed
    1. Baranes D., Lederfein D., Huang Y. Y., Chen M., Bailey C. H., Kandel E. R. (1998). Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21, 813–825. 10.1016/S0896-6273(00)80597-8 - DOI - PubMed
    1. Benchenane K., Berezowski V., Ali C., Fernandez-Monreal M., Lopez-Atalaya J. P., Brillault J., et al. (2005). Tissue-type plasminogen activator crosses the intact blood-brain barrier by LDL-receptor related protein-mediated transcytosis. Circulation. 5:11. 10.1161/01.CIR.0000163542.48611.A2 - DOI - PubMed
    1. Breteler M. M., van Swieten J. C., Bots M. L., Grobbee D. E., Claus J. J., van den Hout J. H., et al. (1994). Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the rotterdam study. Neurology 44, 1246–1252. 10.1212/WNL.44.7.1246 - DOI - PubMed

LinkOut - more resources