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We will study the influence of ischemic stroke on amyloid pathology and vice versa by evaluating the key players of the neurovascular unit, e.g. the blood brain barrier (BBB). We will employ in-vitro models and amyloid transgenic mouse models and analyze them by imaging techniques. Specifically, we will investigate changes in neuronal networks, their reorganization and alterations of BBB transporter functions, after induction of ischemic stroke. For this we can rely on the expertise of each Partner (1-5) combining pharmacologic biotechnologists, radiopharmacologists, BBB-, imaging-, biomarker- and Alzheimer experts and stroke expertise to perform a multidisciplinary cross-disease analysis.

Prof. Dr. med. Marc Fatar and
Dr. Claudia Borrmann (Department of Neurology, Medical Faculty Mannheim),

Dr. Anne Mahringer and Veronika Chevyreva (Pharmaceutical Technology and Biopharmacy, IPMB).

Heidelberg University, Germany

We use in vitro cell culture models (blood –brain barrier models) to investigate transporter function, endocytosis, Aß-translocation and changes in signaling, which occur after hypoperfusion and impaired Aß-clearance. Subsequently we will transfer the in vitro data using a complimentary CAA mouse stroke model and visualize it via PET and MRI. Additionally, we will start a two center human pilot study with acute stroke patients.

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Prof. Dr. Laurence Fenart,
Prof. De. Fabien Gosselet

(BBB Laboratory, Jean Perrin Science Faculty)

Artois University, Lens, France

The blood-brain barrier (BBB) laboratory from Artois University uses house-made in vitro BBB models for investigating BBB physiology and its role in neurodegenerative diseases (Alzheimer’s and Parkinson diseases, stroke, brain tumor metastasis,…) but also for improving drug delivery to CNS and for providing data in pharmaco-toxicological field and to pharmaceutical companies.

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Prof. Dr. Rick M. Dijkhuizen,
Dr. Romain Goulay
(Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences)

University Medical Center Utrecht, Netherlands

The Biomedical MR Imaging and Spectroscopy Group develops and applies magnetic resonance imaging (MRI) and spectroscopy (MRS) methods to elucidate pathophysiology, recovery mechanisms and treatment effects in preclinical models of brain disorders. Our neuroimaging techniques are combined with behavioral, physiological and histological measurements for optimal translational and correlational studies.

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Prof. Dr. med. Klaus Fassbender, 
Dr. med. Alex Yang Liu, Dr. Yann Decker
(Department of Neurology)

Saarland University, Homburg, Germany

Innate immunity has been abundantly shown to influence the development of Alzheimer’s disease pathology. However its role in the development of cerebral amyloid angiopathy remains unclear. We aim at modifying innate immunity to investigate its potential role in the progression of cerebral amyloid angiopathy in transgenic mouse models of Alzheimer.

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Dr. Mar Hernández-Guillamon,
(The Neurovascular Research Laboratory, Vall d'Hebron Research Institute)

Autonomous University of Barcelona, Spain

We propose to find out relevant molecules involved in the process of vascular beta-amyloid accumulation, acting as natural chaperones or promoters. We will identify new biomarkers using an APP transgenic mice as an experimental model of cerebral β-amyloidosis (through microarray and proteomic analysis). In parallel, altered biomarkers expressed in cerebral vessels from CAA patients will be also underscored.

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