CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology (original) (raw)

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Acknowledgements

The authors are grateful to the participants of the ROS, MAP, CHAP, Harvard Aging Brain Study (HAB) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. Data used in preparation of this article were obtained from the ADNI database (http://adni.loni.ucla.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. We also thank the participants of the Brigham and Women's PhenoGenetic Project. This work is supported by the US National Institutes of Health (grants R01 AG031553, R01 AG30146, R01 AG17917, R01 AG15819, P30 AG10161 and R01 AG11101) and the Illinois Department of Public Health. This work was supported by grants R01 NS067305, RC2 GM093080 and R01 AG043617. E.M.B. receives support from the JDRF, American Diabetes Association, Boston Area Diabetes and Endocrinology Research Center and the Harvard NeuroDiscovery Center.

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Authors and Affiliations

1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
   Elizabeth M Bradshaw, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa, Michelle Lee, Alina Von Korff & Philip L De Jager
2. Department of Neurology, Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, Massachusetts, USA
   Elizabeth M Bradshaw, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa, Michelle Lee & Alina Von Korff
3. Harvard Medical School, Boston, Massachusetts, USA
   Elizabeth M Bradshaw, Lori B Chibnik, Linda Ottoboni, Towfique Raj, Keith Johnson & Reisa A Sperling
4. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
   Elizabeth M Bradshaw, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa & Philip L De Jager
5. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA
   Martha C Morris, Julie A Schneider & David A Bennett
6. Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois, USA
   Denis A Evans
7. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
   Keith Johnson & Reisa A Sperling
8. Department of Neurology, Center for Alzheimer's Research and Treatment, Brigham and Women's Hospital, Boston, Massachusetts, USA
   Reisa A Sperling
9. The Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA
   Keith Johnson & Reisa A Sperling

Authors

1. Elizabeth M Bradshaw
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2. Lori B Chibnik
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3. Brendan T Keenan
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4. Linda Ottoboni
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5. Towfique Raj
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6. Anna Tang
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7. Laura L Rosenkrantz
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8. Selina Imboywa
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9. Michelle Lee
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10. Alina Von Korff
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11. Martha C Morris
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12. Denis A Evans
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13. Keith Johnson
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14. Reisa A Sperling
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15. Julie A Schneider
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16. David A Bennett
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17. Philip L De Jager
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The Alzheimer Disease Neuroimaging Initiative

Contributions

E.M.B. and P.L.D. designed and implemented the study. E.M.B. developed the experimental methods using peripheral blood mononuclear cells (PBMCs). E.M.B., L.O., A.T., L.L.R. and S.I. isolated PBMCs from the PhenoGenetic cohort and analyzed monocyte CD33 expression. E.M.B., A.T. and L.L.R. analyzed the uptake ability of monocytes. T.R., B.T.K. and L.B.C. performed the statistical analyses and assisted with the interpretation and communication of results. A.V.K., M.L. and P.L.D. coordinated the collection of blood from the PhenoGenetic cohort. R.A.S., K.J. and ADNI provided the PiB imaging data and reviewed the manuscript. R.A.S. provided the HAB blood samples. M.C.M. contributed post-mortem data on brain microglia and reviewed the manuscript. D.A.E. provided clinical data and biospecimens. J.A.S. was responsible for the microglia and Alzheimer's disease pathology data collection from the brains of deceased MAP participants and revised the manuscript. D.A.B. contributed ante-mortem biospecimens, clinical and post-mortem data, and revised the manuscript. P.L.D. conceived the study, coordinated access to all of the cohorts and wrote the manuscript with E.M.B.

Corresponding author

Correspondence toPhilip L De Jager.

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The authors declare no competing financial interests.

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Bradshaw, E., Chibnik, L., Keenan, B. et al. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.Nat Neurosci 16, 848–850 (2013). https://doi.org/10.1038/nn.3435

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• Received: 19 March 2013
• Accepted: 14 May 2013
• Published: 23 May 2013
• Issue Date: July 2013
• DOI: https://doi.org/10.1038/nn.3435