title: Blood platelets in the progression of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA). Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß) peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS) and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.
authors.affiliation: Department of Clinical and Experimental Hemostasis, Hemotherapy and Transfusion Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Nina S
authors.initials: NS
authors.lastname: Gowert
authors.affiliation: Department of Clinical and Experimental Hemostasis, Hemotherapy and Transfusion Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Lili
authors.initials: L
authors.lastname: Donner
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Department of Cellular Neurology, Hertie-Institut for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany ; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Yvonne S
authors.initials: YS
authors.lastname: Eisele
authors.affiliation: Department of Physiology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Seyda T
authors.initials: ST
authors.lastname: Towhid
authors.affiliation: Department of Physiology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Münzer
authors.affiliation: Department of Physiology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Walker
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ogorek
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität, Tübingen, Germany ; Department of Physiology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.affiliation: Institut für Pharmakologie u. Klinische Pharmakologie, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Grandoch
authors.affiliation: Department of Dermatology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.affiliation: Institut für Pharmakologie u. Klinische Pharmakologie, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Weggen
authors.affiliation: Department of Physiology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Department of Cellular Neurology, Hertie-Institut for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
authors.affiliation: Department of Clinical and Experimental Hemostasis, Hemotherapy and Transfusion Medicine, Heinrich-Heine-University, Düsseldorf, Germany ; Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Elvers
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D016657:Cerebral Amyloid Angiopathy / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species