Plasma Fibrinogen Is a Natural Deterrent to Amyloid Beta-Induced Platelet Activation.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by extensive loss of neurons, and deposition of amyloid beta (Aβ) in the form of extracellular plaques. Aβ is considered to have 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, 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 RhoA-dependent manner. In the present 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 like secretion, clot retraction, rise in cytosolic Ca+2and reactive oxygen species (ROS). Fibrinogen prevented intracellular accumulation of full length amyloid beta 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.
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Vijay
V
Sonkar
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Paresh P
PP
Kulkarni
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Susheel N
SN
Chaurasia
Indian Institute of Science Education and Research, Kolkata, India.
Ayusman
A
Dash
Developmental Toxicology Division, Indian Institute of Toxicological Research, Lucknow, Uttar Pradesh, India.
Abhishek
A
Jauhari
Developmental Toxicology Division, Indian Institute of Toxicological Research, Lucknow, Uttar Pradesh, India.
Devendra
D
Parmar
Developmental Toxicology Division, Indian Institute of Toxicological Research, Lucknow, Uttar Pradesh, India.
Sanjay
S
Yadav
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Debabrata
D
Dash
Alzheimer Disease; Amyloid beta-peptide; clot retraction; fibrinogen; thrombosis