Dataset Title:
Data from: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models

Authors:
Jean C. Cruz Hernández, Oliver Bracko, Calvin J. Kersbergen, Victorine Muse, Mohammad Haft-Javaherian, Maxime Berg, Laibaik Park, Lindsay K. Vinarcsik, Iryna Ivasyk, Daniel A. Rivera, Yiming Kang, Marta Cortes-Canteli, Myriam Peyrounette, Vincent Doyeux, Amy Smith, Joan Zhou, Gabriel Otte, Jeffrey D. Beverly, Elizabeth Davenport, Yohan Davit, Charles P. Lin, Sidney Strickland, Costantino Iadecola, Sylvie Lorthois, Nozomi Nishimura and Chris B. Schaffer

Keywords: 
Cerebral blood flow, Alzheimer’s disease, and cognition

Abstract:
Cerebral blood flow (CBF) reductions in Alzheimer’s disease (AD) patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences on AD pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to neutrophils that adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. This study identified a novel cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of AD and demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a novel strategy for improving cognition in AD patients.. This dataset supports the above research and conclusions

License: These data are shared under a Creative Commons Attribution 4.0 International (CC BY 4.0) License. https://creativecommons.org/licenses/by/4.0/. 

Citation: If you use these data, please cite the original authors. Suggested citation: Hernandez, et al. (2019). Data from: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models [Dataset]. Cornell University Library eCommons Repository. https://doi.org/10.7298/9PR3-D773.

Related Publication: 
Cruz Hernández, J. C. et al. Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models. Nat. Neurosci. (2019). doi:10.1038/s41593-018-0329-4


Funding: 
This work was supported by the National Institutes of Health grants Nos. AG049952
(C.B.S.), NS37853 (CI) and AG031620 (N.N.), the Alzheimer’s Drug Discovery
Foundation (C.B.S.), the Alzheimer’s Art Quilt Initiative (C.B.S.), the BrightFocus
Foundation (C.B.S.), European Research Council grant No. 615102 (S.L.), the DFG
German Research Foundation (O.B.), a National Science Foundation Graduate Research
Fellowship (J.C.H.), the L’Oréal Fellowship for Women in Science (N.N.) and used
computing resources at CALMIP (S.L.).

Corresponding authors email address: Chris B Schaffer (cs385@cornell.edu)
Second contact: Nozomi Nishimura (nn62@cornell.edu)

Data Description:
Data are TIFF or BMP files of 3D in vivo multiphoton images of brain vasculature in combination with additional labeling dyes. All flow cytometry data is uploaded as raw FlowJo (v10.5.1 and 10.5.3)  files and the modified versions.  All mouse data information is stored as CVS or Microsoft Excel files. The statistical analyses files are done either in GraphPad Prism (v7),  R,  or MATLAB (v9.1 and 9.4)