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Longitudinal PET-MRI reveals beta-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion

Maier, FC and Wehrl, HF and Schmid, AM and Mannheim, JG and Wiehr, S and Lerdkrai, C and Calaminus, C and Stahlschmidt, A and Ye, L and Burnet, M and Stiller, D and Sabri, O and Reischl, G and Staufenbiel, M and Garaschuk, O and Jucker, M and Pichler, BJ (2014) Longitudinal PET-MRI reveals beta-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion. Nature Medicine . pp. 1485-1492.

Abstract

The dynamics of beta-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of beta-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral beta-amyloid angiopathy (CAA), beta-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of beta-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal beta-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA

Item Type: Article
Additional Information: NIBR author: Staufenbiel, M institute: NIBR contributor address: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyInstitute of Physiology II, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tubingen, and DZNE, German Center for Neurodegenerative Diseases, Tubingen, GermanySynovo GmbH, Tubingen, GermanyTarget Discovery Research, Boehringer Ingelheim Pharma GmbH &Co. KG, Ingelheim, GermanyDepartment of Nuclear Medicine, University of Leipzig, Leipzig, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, GermanyNovartis Institutes for BioMedical Research, Basel, SwitzerlandInstitute of Physiology II, Eberhard Karls University Tubingen, Tubingen, GermanyDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tubingen, and DZNE, German Center for Neurodegenerative Diseases, Tubingen, GermanyWerner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tubingen, Tubingen, Germany
Date Deposited: 13 Oct 2015 13:11
Last Modified: 13 Oct 2015 13:11
URI: https://oak.novartis.com/id/eprint/24934

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