Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease

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Standard

Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. / Gerrits, Emma; Brouwer, Nieske; Kooistra, Susanne M.; Woodbury, Maya E.; Vermeiren, Yannick; Lambourne, Mirjam; Mulder, Jan; Kummer, Markus; Möller, Thomas; Biber, Knut; Dunnen, Wilfred F.A.den; De Deyn, Peter P.; Eggen, Bart J.L.; Boddeke, Erik W.G.M.

I: Acta Neuropathologica, Bind 141, 2021, s. 681–696.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Gerrits, E, Brouwer, N, Kooistra, SM, Woodbury, ME, Vermeiren, Y, Lambourne, M, Mulder, J, Kummer, M, Möller, T, Biber, K, Dunnen, WFAD, De Deyn, PP, Eggen, BJL & Boddeke, EWGM 2021, 'Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease', Acta Neuropathologica, bind 141, s. 681–696. https://doi.org/10.1007/s00401-021-02263-w

APA

Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., Dunnen, W. F. A. D., De Deyn, P. P., Eggen, B. J. L., & Boddeke, E. W. G. M. (2021). Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. Acta Neuropathologica, 141, 681–696. https://doi.org/10.1007/s00401-021-02263-w

Vancouver

Gerrits E, Brouwer N, Kooistra SM, Woodbury ME, Vermeiren Y, Lambourne M o.a. Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. Acta Neuropathologica. 2021;141:681–696. https://doi.org/10.1007/s00401-021-02263-w

Author

Gerrits, Emma ; Brouwer, Nieske ; Kooistra, Susanne M. ; Woodbury, Maya E. ; Vermeiren, Yannick ; Lambourne, Mirjam ; Mulder, Jan ; Kummer, Markus ; Möller, Thomas ; Biber, Knut ; Dunnen, Wilfred F.A.den ; De Deyn, Peter P. ; Eggen, Bart J.L. ; Boddeke, Erik W.G.M. / Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. I: Acta Neuropathologica. 2021 ; Bind 141. s. 681–696.

Bibtex

@article{b770651c2faa46128e9168acef0c845a,
title = "Distinct amyloid-β and tau-associated microglia profiles in Alzheimer{\textquoteright}s disease",
abstract = "Alzheimer{\textquoteright}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.",
keywords = "Alzheimer{\textquoteright}s disease, Amyloid-β, Microglia, Single-nucleus RNA sequencing, Tau",
author = "Emma Gerrits and Nieske Brouwer and Kooistra, {Susanne M.} and Woodbury, {Maya E.} and Yannick Vermeiren and Mirjam Lambourne and Jan Mulder and Markus Kummer and Thomas M{\"o}ller and Knut Biber and Dunnen, {Wilfred F.A.den} and {De Deyn}, {Peter P.} and Eggen, {Bart J.L.} and Boddeke, {Erik W.G.M.}",
year = "2021",
doi = "10.1007/s00401-021-02263-w",
language = "English",
volume = "141",
pages = "681–696",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease

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

AU - Möller, Thomas

AU - Biber, Knut

AU - Dunnen, Wilfred F.A.den

AU - De Deyn, Peter P.

AU - Eggen, Bart J.L.

AU - Boddeke, Erik W.G.M.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - Amyloid-β

KW - Microglia

KW - Single-nucleus RNA sequencing

KW - Tau

U2 - 10.1007/s00401-021-02263-w

DO - 10.1007/s00401-021-02263-w

M3 - Journal article

C2 - 33609158

AN - SCOPUS:85101223363

VL - 141

SP - 681

EP - 696

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

ER -

ID: 257870995