Accepted for Publication: August 16, 2011.
Published Online: October 10, 2011. doi:10.1001/archneurol.2011.1538
Author Contributions:Study concept and design: Ostrowitzki, Deptula, Bohrmann, Brooks, Ashford, Xu, and Santarelli. Acquisition of data: Deptula, Thurfjell, Barkhof, Bohrmann, and Xu. Analysis and interpretation of data: Ostrowitzki, Deptula, Thurfjell, Barkhof, Bohrmann, Brooks, Klunk, Yoo, Loetscher, and Santarelli. Drafting of the manuscript: Ostrowitzki, Deptula, Thurfjell, Bohrmann, Ashford, Yoo, and Santarelli. Critical revision of the manuscript for important intellectual content: Ostrowitzki, Deptula, Barkhof, Brooks, Klunk, Xu, Loetscher, and Santarelli. Statistical analysis: Yoo. Obtained funding: Santarelli. Administrative, technical, and material support: Ostrowitzki, Deptula, Bohrmann, Ashford, Loetscher, and Santarelli. Study supervision: Ostrowitzki, Deptula, Brooks, and Ashford.
Financial Disclosure: Drs Ostrowitzki, Deptula, Bohrmann, Ashford, Yoo, Xu, Loetscher, and Santarelli are full-time employees of Roche/F. Hoffmann–La Roche Ltd, and they may additionally hold Roche stock/stock options. Dr Thurfjell is a full-time employee of GE Healthcare. Dr Barkhof is receiving consultancy fees from pharmaceutical companies, including F. Hoffmann–La Roche Ltd. Dr Brooks holds a part-time position as a Senior Neurologist with GE Healthcare, which holds a license agreement with the University of Pittsburgh based on the [11C]PiB PET technology described in this study. Dr Klunk is the coinventor of this technology and, as such, has a financial interest in this license agreement. GE Healthcare has provided grant support and consultant fees to Dr Klunk for studies unrelated to this work, and Dr Klunk has received consultant fees/honoraria related to this study from Roche. During the past 12 months, Dr Brooks has received consultancy fees from Synosia, Schering Plough, Amsterdam Molecular Therapeutics, Biogen Idec, NeuroNova, Shire, Genentech, and Janssen and honoraria from Teva, UCB, GlaxoSmithKline, and Orion Pharma.
Funding/Support: This work was supported by F. Hoffmann–La Roche Ltd.
Additional Contributions: We thank the following investigators for supporting this PET study: Niels Andreasen, MD (Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden), Roger Bullock, MD (Kingshill Research Centre, Swindon, England), Mark Dale, MD (Memory Assessment Centre, Blackpool, England), Adriaan Lammertsma, PhD (Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, Netherlands), and Philip Scheltens, MD (Alzheimer Centre, VU University Medical Center, Amsterdam, Netherlands). We also thank the following Roche employees: Sumu Sethi, PhD, for her role in monitoring the study conduct, and Françoise Gerber, Krisztina Oroszlan, and Juerg Messer for their support in brain sectioning, in performing immunohistochemical stainings, confocal microscopy, and autoradiography. We thank Ursula Puentener, PhD, for isolating and enriching primary human microglia cells. We especially thank the patients and their caregivers for their participation in this study.