The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer’s Disease

Akhter H, Huang WT, van Groen T, Kuo HC, Miyata T, Liu RM (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 Alzheimers Dis 64 (2):447–457. https://doi.org/10.3233/jad-180241

Article  CAS  PubMed  Google Scholar 

Alam JJ, Nixon RA (2023) Drug development targeting degeneration of the basal forebrain cholinergic system: its time has come. Mol Neurodegener 18 (1):74. https://doi.org/10.1186/s13024-023-00663-y

Article  PubMed  PubMed Central  Google Scholar 

Ali NH, Al-Kuraishy HM, Al-Gareeb AI, Alnaaim SA, Alexiou A, Papadakis M, Saad HM, Batiha GE (2024) The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer’s disease: a new perspective. Acta Neurol Belg 124 (2):377–388. https://doi.org/10.1007/s13760-023-02403-x

Article  PubMed  Google Scholar 

Angelucci F, Čechová K, Průša R, Hort J (2019) Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: consequences on extracellular maturation of brain-derived neurotrophic factor and therapeutic implications. CNS Neurosci Ther 25 (3):303–313. https://doi.org/10.1111/cns.13082

Article  CAS  PubMed  Google Scholar 

Angelucci F, Veverova K, Katonová A, Piendel L, Vyhnalek M, Hort J (2022) Alzheimer’s disease severity is associated with an imbalance in serum levels of enzymes regulating plasmin synthesis. Pharmaceuticals (Basel). https://doi.org/10.3390/ph15091074

Article  PubMed  PubMed Central  Google Scholar 

Angelucci F, Veverova K, Katonová A, Vyhnalek M, Hort J (2023) Serum PAI-1/BDNF ratio is increased in Alzheimer’s disease and correlates with disease severity. ACS Omega 8 (39):36025–36031. https://doi.org/10.1021/acsomega.3c04076

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baker SK, Chen ZL, Norris EH, Revenko AS, MacLeod AR, Strickland S (2018) Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 115 (41):E9687-e9696. https://doi.org/10.1073/pnas.1811172115

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baker SK, Chen ZL, Norris EH, Strickland S (2019) Plasminogen mediates communication between the peripheral and central immune systems during systemic immune challenge with lipopolysaccharide. J Neuroinflammation 16 (1):172. https://doi.org/10.1186/s12974-019-1560-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ben-Nejma IRH, Keliris AJ, Vanreusel V, Ponsaerts P, Van der Linden A, Keliris GA (2023) Altered dynamics of glymphatic flow in a mature-onset Tet-off APP mouse model of amyloidosis. Alzheimers Res Ther 15 (1):23. https://doi.org/10.1186/s13195-023-01175-z

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blackmon TJ, MacMahon JA, Bernardino PN, Hogans RE, Cheng MY, Vu J, Lee RD, Saito NH, Grodzki AC, Bruun DA, Wulff H, Woolard KD, Brooks-Kayal A, Harvey DJ, Gorin FA, Lein PJ (2025) Spatiotemporal perturbations of the plasminogen activation system in a rat model of acute organophosphate intoxication. Acta Neuropathol Commun 13 (1):62. https://doi.org/10.1186/s40478-025-01979-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Briggs CA, Chakroborty S, Stutzmann GE (2017) Emerging pathways driving early synaptic pathology in alzheimer’s disease. Biochem Biophys Res Commun 483 (4):988–997. http://doi.org/https://doi.org/https://doi.org/10.1016/j.bbrc.2016.09.088

Article  CAS  PubMed  Google Scholar 

Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI (2015) The involvement of BDNF, NGF and GDNF in aging and alzheimer’s disease. Aging Dis 6 (5):331–341. https://doi.org/10.14336/ad.2015.0825

Article  PubMed  PubMed Central  Google Scholar 

Casquero-Veiga M, Ceron C, Cortes-Canteli M (2025) Alzheimer’s disease and vascular biology - A focus on the procoagulant state. Curr Opin Cell Biol 95:102528. https://doi.org/10.1016/j.ceb.2025.102528

Article  CAS  PubMed  Google Scholar 

Chen J, Zhang T, Jiao S, Zhou X, Zhong J, Wang Y, Liu J, Deng J, Wang S, Xu Z (2017) ProBDNF accelerates brain Amyloid-β deposition and learning and memory impairment in APPswePS1dE9 Transgenic mice. J Alzheimers Dis 59 (3):941–949. https://doi.org/10.3233/jad-161191

Article  CAS  PubMed  Google Scholar 

Chen SH, He CY, Shen YY, Zeng GH, Tian DY, Cheng Y, Xu MY, Fan DY, Tan CR, Shi AY, Bu XL, Wang YJ (2022) Polysaccharide Krestin prevents alzheimer’s Disease-type pathology and cognitive deficits by enhancing monocyte Amyloid-β processing. Neurosci Bull 38 (3):290–302. https://doi.org/10.1007/s12264-021-00779-5

Article  CAS  PubMed  Google Scholar 

Chen ZL, Singh PK, Calvano M, Norris EH, Strickland S (2023) A possible mechanism for the enhanced toxicity of beta-amyloid protofibrils in alzheimer’s disease. Proc Natl Acad Sci U S A 120 (36):e2309389120. https://doi.org/10.1073/pnas.2309389120

Article  CAS  PubMed  PubMed Central  Google Scholar 

Choudhury A, Prabha S, Saeed MU, Mohammad T, Hussain A, AlAjmi MF, Khan FI, Islam A, Hassan MI (2025) Targeting Tau hyperphosphorylation-mediated neuroinflammation in alzheimer’s disease via ABL1 kinase inhibition: insights from microsecond MD simulation and MM/PBSA analyses. Int J Biol Macromol 320 (Pt 2):145785. https://doi.org/10.1016/j.ijbiomac.2025.145785

Article  CAS  PubMed  Google Scholar 

Cummings J, Apostolova L, Rabinovici GD, Atri A, Aisen P, Greenberg S, Hendrix S, Selkoe D, Weiner M, Petersen RC, Salloway S (2023) Lecanemab: appropriate use recommendations. J Prev Alzheimer’s Disease 10 (3):362–377. https://doi.org/10.14283/jpad.2023.30

Article  CAS  Google Scholar 

Daly T, Houot M, Barberousse A, Agid Y, Epelbaum S (2020) Amyloid-β in Alzheimer’s disease: a study of citation practices of the amyloid cascade hypothesis between 1992 and 2019. J Alzheimers Dis 74 (4):1309–1317. https://doi.org/10.3233/jad-191321

Article  PubMed  Google Scholar 

de Oliveira J, Kucharska E, Garcez ML, Rodrigues MS, Quevedo J, Moreno-Gonzalez I, Budni J (2021) Inflammatory cascade in Alzheimer’s disease pathogenesis: a review of experimental findings. Cells. https://doi.org/10.3390/cells10102581

Article  PubMed  PubMed Central  Google Scholar 

Diaz A, Merino P, Guo JD, Yepes MA, McCann P, Katta T, Tong EM, Torre E, Rangaraju S, Yepes M (2020) Urokinase-type plasminogen activator protects cerebral cortical neurons from soluble Aβ-induced synaptic damage. J Neurosci 40 (21):4251–4263. https://doi.org/10.1523/jneurosci.2804-19.2020

Article  CAS  PubMed  PubMed Central  Google Scholar 

Do Carmo S, Kannel B, Cuello AC (2021) The nerve growth factor metabolic pathway dysregulation as cause of Alzheimer’s cholinergic atrophy. Cells. https://doi.org/10.3390/cells11010016

Article  PubMed  PubMed Central  Google Scholar 

Drewes G, Trinczek B, Illenberger S, Biernat J, Schmitt-Ulms G, Meyer HE, Mandelkow EM, Mandelkow E (1995) Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site Serine 262. J Biol Chem 270 (13):7679–7688. https://doi.org/10.1074/jbc.270.13.7679

Article  CAS  PubMed  Google Scholar 

Dubey S, Heinen S, Krantic S, McLaurin J, Branch DR, Hynynen K, Aubert I (2020) Clinically approved IVIg delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer’s disease. Proc Natl Acad Sci U S A 117 (51):32691–32700. https://doi.org/10.1073/pnas.1908658117

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eruysal E, Iadecola C, Ishii M (2022) Circulating plasminogen activator inhibitor-1 (PAI-1) levels in the preclinical stage of Alzheimer’s disease. Alzheimers Dement 18 (S5):e067353. https://doi.org/10.1002/alz.067353

Article  Google Scholar 

Esser N, Hogan MF, Templin AT, Akter R, Fountaine BS, Castillo JJ, El-Osta A, Manathunga L, Zhyvoloup A, Raleigh DP, Zraika S, Hull RL, Kahn SE (2024) The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity. Diabetologia 67 (9):1897–1911. https://doi.org/10.1007/s00125-024-06161-0

Article  CAS  PubMed 

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