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Distinct amyloid-β ...
Distinct amyloid-β and tau-associated microglia profiles in Alzheimer's disease
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Gerrits, E (författare)
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Brouwer, N (författare)
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Kooistra, SM (författare)
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Woodbury, ME (författare)
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Vermeiren, Y (författare)
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Lambourne, M (författare)
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- Mulder, J (författare)
- Karolinska Institutet
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Kummer, M (författare)
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Moller, T (författare)
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Biber, K (författare)
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den Dunnen, WFA (författare)
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De Deyn, PP (författare)
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Eggen, BJL (författare)
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Boddeke, EWGM (författare)
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(creator_code:org_t)
- 2021-02-20
- 2021
- Engelska.
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 141:5, s. 681-696
- Relaterad länk:
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https://link.springe...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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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Till lärosätets databas
- Av författaren/redakt...
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Gerrits, E
-
Brouwer, N
-
Kooistra, SM
-
Woodbury, ME
-
Vermeiren, Y
-
Lambourne, M
-
visa fler...
-
Mulder, J
-
Kummer, M
-
Moller, T
-
Biber, K
-
den Dunnen, WFA
-
De Deyn, PP
-
Eggen, BJL
-
Boddeke, EWGM
-
visa färre...
- Artiklar i publikationen
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Acta neuropathol ...
- Av lärosätet
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Karolinska Institutet