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Nat Med. 2014 Dec;20(12):1485-92. doi: 10.1038/nm.3734. Epub 2014 Nov 10.

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

Author information

1
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
2
Institute of Physiology II, Eberhard Karls University Tübingen, Tübingen, Germany.
3
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
4
Synovo GmbH, Tübingen, Germany.
5
Target Discovery Research, Boehringer Ingelheim Pharma GmbH &Co. KG, Ingelheim, Germany.
6
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
7
Novartis Institutes for BioMedical Research, Basel, Switzerland.

Abstract

The dynamics of β-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 β-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 β-amyloid angiopathy (CAA), β-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of β-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal β-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.

PMID:
25384087
DOI:
10.1038/nm.3734
[Indexed for MEDLINE]

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