Platelet Proteomic Analysis Revealed Differential Pattern of Cytoskeletal- and Immune-Related Proteins at Early Stages of Alzheimer’s Disease
Platelets are considered a good model system to study a number of elements associated with neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Peripheral blood platelet alterations including cytoskeletal abnormalities, abnormal cytoplasmic calcium fluxes or increased oxidative stress levels have been related to Alzheimer’s disease (AD) pathology. Therefore, platelets can be considered a peripheral model to study metabolic mechanisms occurring in AD. To investigate peripheral molecular alterations, we examined platelet protein expression in a cohort of 164 subjects, including mild cognitive impairment (MCI), and AD patients, and healthy aged-matched controls. A two-dimensional difference gel electrophoresis (2D-DIGE) discovery phase revealed significant differences between patients and controls in five proteins: talin, vinculin, moesin, complement C3b and Rho GDP, which are known to be involved in cytoskeletal regulation including focal adhesions, inflammation and immune functions. Western blot analysis verified that talin was found to be increased in mild and moderate AD groups versus control, while the other three were found to be decreased. We also analysed amyloid precursor protein (APP), amyloid-β 1-40 (Aβ40) and 1-42 (Aβ42) levels in platelets from the same groups of subjects. Upregulation of platelet APP and Aβ peptides was found in AD patients compared to controls. These findings complement and expand previous reports concerning the morphological and functional alterations in AD platelets, and provide more insights into possible mechanisms that participate in the multifactorial and systemic damage in AD.
KeywordsAlzheimer’s disease Platelets Cytoskeletal proteins Amyloid-β Peripheral changes Amyloid precursor protein
We are grateful to the patients and donors without which this work would not have been possible. We also thank the i+12 Proteomic Unit, in particular Ines Garcia-Consuegra for her advice in the proteomic analysis. We also thank Lola Gutierrez from the UCM CAI-Proteomic Unit helping to analyse and understand the 2D-DIGE results.
This study was supported by grants from the Instituto de Salud Carlos III (PI12/00486; CM15/00222; PI15/00780), FEDER, and CIBERNED.
Compliance with Ethical Standards
Conflict of Interest
The authors declare they have no conflict of interest.
Ethical Approval and Informed Consent
Blood samples were obtained through antecubital vein puncture. Donors gave written consent, in accordance with the Declaration of Helsinki and the project was approved by the local ethical review committee from the Research Institute Hospital 12 de Octubre (i+12).
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