Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion.
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.
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Florian C
FC
Maier
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Hans F
HF
Wehrl
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Andreas M
AM
Schmid
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Julia G
JG
Mannheim
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Stefan
S
Wiehr
Institute of Physiology II, Eberhard Karls University Tübingen, Tübingen, Germany.
Chommanad
C
Lerdkrai
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Carsten
C
Calaminus
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Anke
A
Stahlschmidt
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
Lan
L
Ye
Synovo GmbH, Tübingen, Germany.
Michael
M
Burnet
Target Discovery Research, Boehringer Ingelheim Pharma GmbH &Co. KG, Ingelheim, Germany.
Detlef
D
Stiller
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Osama
O
Sabri
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Gerald
G
Reischl
Novartis Institutes for BioMedical Research, Basel, Switzerland.
Mathias
M
Staufenbiel
Institute of Physiology II, Eberhard Karls University Tübingen, Tübingen, Germany.
Olga
O
Garaschuk
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
Mathias
M
Jucker
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Bernd J
BJ
Pichler
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000814:Aniline Compounds; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000473:pathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005260:Female; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D064847:Multimodal Imaging; D055420:Perfusion Imaging; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D052160:Benzothiazoles; D019275:Radiopharmaceuticals; D013844:Thiazoles