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

被引：97

作者：

Maier, Florian C. ^{[1
]}

Wehrl, Hans F. ^{[1
]}

Schmid, Andreas M. ^{[1
]}

Mannheim, Julia G. ^{[1
]}

Wiehr, Stefan ^{[1
]}

Lerdkrai, Chommanad ^{[2
]}

Calaminus, Carsten ^{[1
]}

Stahlschmidt, Anke ^{[1
]}

Ye, Lan ^{[3
,4
]}

Burnet, Michael ^{[5
]}

Stiller, Detlef ^{[6
]}

Sabri, Osama ^{[7
]}

Reischl, Gerald ^{[1
]}

Staufenbiel, Mathias ^{[8
]}

Garaschuk, Olga ^{[2
]}

Jucker, Mathias ^{[3
,4
]}

Pichler, Bernd J. ^{[1
]}

机构：

[1] Univ Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Imaging Ctr, Tubingen, Germany

[2] Univ Tubingen, Inst Physiol 2, Tubingen, Germany

[3] Univ Tubingen, Dept Cellular Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

[4] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany

[5] Synovo GmbH, Tubingen, Germany

[6] Boehringer Ingelheim Pharma GmbH & Co KG, Target Discovery Res, Ingelheim, Germany

[7] Univ Leipzig, Dept Nucl Med, D-04109 Leipzig, Germany

[8] Novartis Inst BioMed Res, Basel, Switzerland

来源：

NATURE MEDICINE | 2014年 / 20卷 / 12期

关键词：

POSITRON-EMISSION-TOMOGRAPHY; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; HYPOTHETICAL MODEL; A-BETA; MICE; BRAIN; PLAQUES; GROWTH; IMPAIRMENT;

D O I：

10.1038/nm.3734

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 p-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.

引用

页码：1485 / 1492

页数：8

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