CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology

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; Martha C. Morris; Denis A. Evans; Keith Johnson; Reisa A. Sperling; Julie A. Schneider; David A. Bennett; Philip L. De Jager

doi:10.1038/nn.3435

CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology

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, Martha C. Morris, Denis A. Evans, Keith Johnson, Reisa A. Sperling, Julie A. Schneider, David A. Bennett, Philip L. De Jager

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457 Scopus citations

Abstract

In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444C risk allele was associated with greater cell surface expression of CD33 in the monocytes (t₅₀ = 10.06, P _joint = 1.3 × 10^-13) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

Original language	English
Pages (from-to)	848-850
Number of pages	3
Journal	Nature Neuroscience
Volume	16
Issue number	7
DOIs	https://doi.org/10.1038/nn.3435
State	Published - Jul 2013
Externally published	Yes

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Bradshaw, E. M., Chibnik, L. B., Keenan, B. T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L. L., Imboywa, S., Lee, M., Von Korff, A., Morris, M. C., Evans, D. A., Johnson, K., Sperling, R. A., Schneider, J. A., Bennett, D. A., & De Jager, P. L. (2013). CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology. Nature Neuroscience, 16(7), 848-850. https://doi.org/10.1038/nn.3435

@article{8085b058ba624118b19d652cb4d41c20,

title = "CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology",

abstract = "In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444C risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P joint = 1.3 × 10-13) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.",

author = "Bradshaw, {Elizabeth M.} and Chibnik, {Lori B.} and Keenan, {Brendan T.} and Linda Ottoboni and Towfique Raj and Anna Tang and Rosenkrantz, {Laura L.} and Selina Imboywa and Michelle Lee and {Von Korff}, Alina and Morris, {Martha C.} and Evans, {Denis A.} and Keith Johnson and Sperling, {Reisa A.} and Schneider, {Julie A.} and Bennett, {David A.} and {De Jager}, {Philip L.}",

note = "Funding Information: The authors are grateful to the participants of the ROS, MAP, CHAP, Harvard Aging Brain Study (HAB) and Alzheimer{\textquoteright}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{\textquoteright}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.",

year = "2013",

month = jul,

doi = "10.1038/nn.3435",

language = "English",

volume = "16",

pages = "848--850",

journal = "Nature Neuroscience",

issn = "1097-6256",

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Bradshaw, EM, Chibnik, LB, Keenan, BT, Ottoboni, L, Raj, T, Tang, A, Rosenkrantz, LL, Imboywa, S, Lee, M, Von Korff, A, Morris, MC, Evans, DA, Johnson, K, Sperling, RA, Schneider, JA, Bennett, DA & De Jager, PL 2013, 'CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology', Nature Neuroscience, vol. 16, no. 7, pp. 848-850. https://doi.org/10.1038/nn.3435

TY - JOUR

T1 - CD33 Alzheimer's disease locus

T2 - Altered monocyte function and amyloid biology

AU - Bradshaw, Elizabeth M.

AU - Chibnik, Lori B.

AU - Keenan, Brendan T.

AU - Ottoboni, Linda

AU - Raj, Towfique

AU - Tang, Anna

AU - Rosenkrantz, Laura L.

AU - Imboywa, Selina

AU - Lee, Michelle

AU - Von Korff, Alina

AU - Morris, Martha C.

AU - Evans, Denis A.

AU - Johnson, Keith

AU - Sperling, Reisa A.

AU - Schneider, Julie A.

AU - Bennett, David A.

AU - De Jager, Philip L.

N1 - Funding Information: 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.

PY - 2013/7

Y1 - 2013/7

N2 - In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444C risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P joint = 1.3 × 10-13) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

AB - In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444C risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P joint = 1.3 × 10-13) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

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DO - 10.1038/nn.3435

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AN - SCOPUS:84891706947

SN - 1097-6256

VL - 16

SP - 848

EP - 850

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 7

ER -

CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology

Abstract

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