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Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models.

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Title: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models.
Authors: Cruz Hernández, Jean C., Bracko, Oliver, Kersbergen, Calvin J., Muse, Victorine, Haft-Javaherian, Mohammad, Berg, Maxime, Park, Laibaik, Vinarcsik, Lindsay K., Ivasyk, Iryna, Rivera, Daniel A., Kang, Yiming, Cortes-Canteli, Marta, Peyrounette, Myriam, Doyeux, Vincent, Smith, Amy, Zhou, Joan, Otte, Gabriel, Beverly, Jeffrey D., Davenport, Elizabeth, Davit, Yohan
Source: Nature Neuroscience. Mar2019, Vol. 22 Issue 3, p413-420. 8p. 6 Graphs.
Abstract: Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer's disease 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 in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer's disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer's disease patients. The authors found that white blood cells plug about 2% of capillaries in the brains of Alzheimer's disease mouse models. When the adhesion of these cells was blocked, cerebral blood flow immediately increased and cognitive performance rapidly improved. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models.
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. Mar2019, Vol. 22 Issue 3, p413-420. 8p. 6 Graphs.
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  Data: Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer's disease 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 in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer's disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer's disease patients. The authors found that white blood cells plug about 2% of capillaries in the brains of Alzheimer's disease mouse models. When the adhesion of these cells was blocked, cerebral blood flow immediately increased and cognitive performance rapidly improved. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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