Plasma Fibrinogen Is a Natural Deterrent to Amyloid β-Induced Platelet Activation and Neuronal Toxicity

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2016-01, Vol.22 (1), p.224-232
• Main Authors: Sonkar, Vijay K, Kulkarni, Paresh P, Chaurasia, Susheel N, Dash, Ayusman, Jauhari, Abhishek, Parmar, Devendra, Yadav, Sanjay, Dash, Debabrata
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino acids; Antibiotics; Antibodies; Binding sites; Blood platelets; Experiments; Flow cytometry; Neuroblastoma; Pathogenesis; Peptides; Proteins; Reactive oxygen species
• ISSN: 1076-1551; 1528-3658
• DOI: 10.2119/molmed.2016.00003

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, characterized by extensive loss of neurons and deposition of amyloid β (Aβ) in the form of extracellular plaques. Aβ is considered to have a critical role in synaptic loss and neuronal death underlying cognitive decline. Platelets contribute to 95% of circulating amyloid precursor protein that releases Aβ into circulation. We have recently demonstrated that the Aβ active fragment containing amino acid sequence 25–35 (Aβ25–35) is highly thrombogenic in nature and elicits strong aggregation of washed human platelets in a RhoA-dependent manner. In this study, we evaluated the influence of fibrinogen on Aβ-induced platelet activation. Intriguingly, Aβ failed to induce aggregation of platelets suspended in plasma but not in buffer. Fibrinogen brought about dose-dependent decline in aggregatory response of washed human platelets elicited by Aβ25–35, which could be reversed by increasing doses of Aβ. Fibrinogen also attenuated Aβ-induced platelet responses such as secretion, clot retraction, rise in cytosolic Ca+2 and reactive oxygen species. Fibrinogen prevented intracellular accumulation of full-length Aβ peptide (Aβ42) in platelets as well as neuronal cells. We conclude that fibrinogen serves as a physiological check against the adverse effects of Aβ by preventing its interaction with cells.