Activation of the factor XII-driven contact system in Alzheimer's disease patient and mouse model plasma

Proceedings of the National Academy of Sciences of the United States of America
Daria ZamolodchikovSidney Strickland

Abstract

Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which likely contributes to disease via multiple mechanisms. Increasing evidence implicates inflammation in AD, the origins of which are not completely understood. We investigated whether circulating Aβ could initiate inflammation in AD via the plasma contact activation system. This proteolytic cascade is triggered by the activation of the plasma protein factor XII (FXII) and leads to kallikrein-mediated cleavage of high molecular-weight kininogen (HK) and release of proinflammatory bradykinin. Aβ has been shown to promote FXII-dependent cleavage of HK in vitro. In addition, increased cleavage of HK has been found in the cerebrospinal fluid of patients with AD. Here, we show increased activation of FXII, kallikrein activity, and HK cleavage in AD patient plasma. Increased contact system activation is also observed in AD mouse model plasma and in plasma from wild-type mice i.v. injected with Aβ42. Our results demonstrate that Aβ42-mediated contact system activation can occur in the AD circulation and suggest new pathogenic mechanisms, diagnostic tests, and therapies for AD.

References

Nov 1, 1975·Journal of Psychiatric Research·M F FolsteinP R McHugh
Jul 3, 1998·Alzheimer Disease and Associated Disorders·L BergamaschiniA Agostoni
Sep 18, 1998·Archives of Neurology·B T Hyman
Jan 13, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Y ShibayamaA P Kaplan
Jun 27, 2000·Neurobiology of Aging·K A Johnson, M S Albert
Feb 13, 2001·Neurobiology of Aging·L BergamaschiniA Agostoni
Jun 21, 2001·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·R A CardiganS J Machin
Sep 8, 2004·Thrombosis and Haemostasis·Hans-Ulrich PauerPeter Burfeind
Aug 12, 2005·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Sofia Ramström
Aug 1, 2006·Nature Genetics·Helen PickersgillBas van Steensel
Apr 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Christian KannemeierKlaus T Preissner
Sep 18, 2007·Neurobiology of Aging·Andrew J Farrall, Joanna M Wardlaw
Jan 19, 2008·Neurotoxicity Research·Rommy von Bernhardi
Jul 29, 2008·Journal of Cellular and Molecular Medicine·Jae K Ryu, James G McLarnon
Aug 30, 2008·The Journal of Clinical Investigation·Coen MaasMartijn F B G Gebbink
Sep 3, 2010·Progress in Molecular Biology and Translational Science·Peter WeiserLijuan Zhang
Sep 3, 2010·Progress in Molecular Biology and Translational Science·Jing PanLijuan Zhang
Nov 30, 2010·Experimental Gerontology·Christian Humpel
Nov 4, 2011·Nature Reviews. Neuroscience·Berislav V Zlokovic
Dec 7, 2011·Neurobiology of Aging·Richard Mayeux, Nicole Schupf
Jan 4, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Stephen F CarterAgneta Nordberg
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Tony Wyss-Coray, Joseph Rogers
Jun 20, 2012·The European Journal of Neuroscience·Pedro M Pimentel-Coelho, Serge Rivest
Jul 31, 2012·Journal of Alzheimer's Disease : JAD·Jack C de la Torre
Aug 15, 2012·Journal of Alzheimer's Disease : JAD·Bob OlssonOskar Hansson
Sep 15, 2012·Journal of Alzheimer's Disease : JAD·Audrey GabelleClaudine Berr
Sep 21, 2012·Blood·Thomas RennéCoen Maas
Oct 2, 2012·Journal of Thrombosis and Haemostasis : JTH·R LoeffenH M H Spronk
Apr 3, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ulrike Träger, Sarah J Tabrizi
Nov 6, 2013·Journal of Neuroinflammation·Ming-Hsuan Ou-Yang, William E Van Nostrand
Jan 28, 2014·Neuron·Joshua E Burda, Michael V Sofroniew
Aug 28, 2014·Journal of Alzheimer's Disease : JAD·Christina E WierengaZvinka Z Zlatar

❮ Previous
Next ❯

Citations

Oct 7, 2015·Frontiers in Cellular Neuroscience·Sophia BardehleKaterina Akassoglou
Nov 29, 2015·Journal of Thrombosis and Haemostasis : JTH·D ZamolodchikovS Strickland
Feb 9, 2017·Scientific Reports·Susanna L LundströmRoman A Zubarev
Apr 6, 2018·Nature Reviews. Neuroscience·Mark A PetersenKaterina Akassoglou
Nov 12, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Katrin F NickelThomas Renné
Nov 6, 2018·Journal of Thrombosis and Haemostasis : JTH·S de MaatC Maas
Feb 2, 2018·The Journal of Clinical Investigation·Sidney Strickland
Oct 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Zu-Lin ChenErin H Norris
Oct 13, 2018·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Hitomi Yamamoto-ImotoSidney Strickland
Jun 2, 2016·Oncotarget·Lu YangYuesheng Zhang
Jul 6, 2016·Current Opinion in Hematology·Alvin H Schmaier
Nov 14, 2015·Journal of Thrombosis and Haemostasis : JTH·Alvin H Schmaier
Feb 23, 2019·Psychogeriatrics : the Official Journal of the Japanese Psychogeriatric Society·Cen SuYaoming Xu
Oct 19, 2019·Research and Practice in Thrombosis and Haemostasis·Alvin H Schmaier, Evi X Stavrou
Sep 15, 2020·Journal of Alzheimer's Disease : JAD·Klaus Grossmann
Nov 17, 2016·International Journal of Hematology·Lisha LinJinhua Zhao
Jul 21, 2020·Research and Practice in Thrombosis and Haemostasis·Nima MazinaniChristian J Kastrup
Sep 17, 2015·Journal of Internal Medicine·E KenneT Renné
Sep 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sarah K BakerSidney Strickland
Sep 12, 2019·Frontiers in Immunology·Coen Maas
Jul 12, 2020·Journal of Alzheimer's Disease : JAD·Pradeep K SinghErin H Norris
Dec 12, 2018·The Journal of Clinical Investigation·Alvin H Schmaier
Feb 22, 2018·Oncotarget·Lu YangYuesheng Zhang
Jan 29, 2016·Journal of Thrombosis and Haemostasis : JTH·A H Schmaier
Jan 11, 2021·Biomarker Research·Jung Eun ParkJung Sup Lee
Nov 13, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Ioanna MarkakiPer Svenningsson
Mar 17, 2020·Neurobiology of Disease·Pradeep K SinghErin H Norris
Jun 11, 2017·Thrombosis Research·Alvin H Schmaier
Mar 23, 2021·Frontiers in Molecular Neuroscience·Nicholas Peoples, Candace Strang
Sep 5, 2020·European Journal of Medicinal Chemistry·Clara DavoineLionel Pochet
Apr 2, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Liu ShiAlejo J Nevado-Holgado
May 6, 2021·International Journal of Molecular Sciences·Klaus Grossmann
May 13, 2021·Research and Practice in Thrombosis and Haemostasis·Pradeep K SinghErin H Norris
Jun 3, 2021·International Journal of Molecular Sciences·Christian StetterChristiane Albert-Weißenberger
Jun 2, 2021·Journal of Thrombosis and Haemostasis : JTH·Eugénie GarnierSara Martinez de Lizarrondo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.