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Emma Gerrits, Nieske Brouwer, Susanne M. Kooistra, Maya E. Woodbury, Yannick Vermeiren, Mirjam Lambourne, Jan Mulder, Markus P. Kummer, Thomas Möller, Knut Biber and 4 more
Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-β and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-β and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-β plaques or both amyloid-β plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-β load and localized to amyloid-β plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies.
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Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M. P., Möller, T., Biber, K., Dunnen, W. F. D., Deyn, P. P. D., Eggen, B. J. L., & Boddeke, E. (2021). Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. Acta Neuropathologica, 141(5), 681–696. https://doi.org/10.1007/s00401-021-02263-w
Gerrits, Emma, et al. "Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease." Acta Neuropathologica, vol. 141, no. 5, 2021, pp. 681–696, https://doi.org/10.1007/s00401-021-02263-w.
Gerrits, Emma, Nieske Brouwer, Susanne M. Kooistra, Maya E. Woodbury, Yannick Vermeiren, Mirjam Lambourne, Jan Mulder, et al. "Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease." Acta Neuropathologica 141, no. 5 (2021): 681–696. https://doi.org/10.1007/s00401-021-02263-w.
Gerrits E., Brouwer N., Kooistra S. M. [и др.] Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease // Acta Neuropathologica. — 2021. — Vol. 141, № 5. — P. 681–696. — URL: https://doi.org/10.1007/s00401-021-02263-w
@article{gerrits2021distinct,
title = {{Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease}},
author = {Emma Gerrits and Nieske Brouwer and Susanne M. Kooistra and Maya E. Woodbury and Yannick Vermeiren and Mirjam Lambourne and Jan Mulder and Markus P. Kummer and Thomas Möller and Knut Biber and Wilfred F.A. den Dunnen and Peter Paul De Deyn and Bart J. L. Eggen and Erik Boddeke},
journal = {Acta Neuropathologica},
year = {2021},
volume = {141},
number = {5},
pages = {681--696},
doi = {10.1007/s00401-021-02263-w},
url = {https://doi.org/10.1007/s00401-021-02263-w}
}TY - JOUR AU - Gerrits, Emma AU - Brouwer, Nieske AU - Kooistra, Susanne M. AU - Woodbury, Maya E. AU - Vermeiren, Yannick AU - Lambourne, Mirjam AU - Mulder, Jan AU - Kummer, Markus P. AU - Möller, Thomas AU - Biber, Knut AU - Dunnen, Wilfred F.A. den AU - Deyn, Peter Paul De AU - Eggen, Bart J. L. AU - Boddeke, Erik TI - Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease JO - Acta Neuropathologica VL - 141 IS - 5 SP - 681 EP - 696 PY - 2021 DA - 2021/02/20 DO - 10.1007/s00401-021-02263-w UR - https://doi.org/10.1007/s00401-021-02263-w ER -
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