000282944 001__ 282944
000282944 005__ 20251218103447.0
000282944 037__ $$aDZNE-2025-01405
000282944 1001_ $$0P:(DE-2719)9001304$$adeWeerd, Lis$$b0$$udzne
000282944 245__ $$aDataset: Chronic Aducanumab-mediated clearance of amyloid plaques decreases microglial activation and induces a unique microglial phenotype associated with antigen presentation
000282944 260__ $$bGene Expression Omnibus$$c2025
000282944 3367_ $$2BibTeX$$aMISC
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000282944 520__ $$aAnti-amyloid β-peptide (Aβ) immune therapy was developed as treatment for Alzheimer’s disease (AD) to reduce and prevent amyloid plaque pathology. This approach has proven successful in phase 3 clinical trials of Aducanumab, Lecanemab and Donanemab. These antibodies induce robust amyloid plaque clearance, slow memory decline, and have beneficial effects on daily living activities. The therapeutic effects correlate with the efficacy of plaque removal. Treatment is associated with adverse side-effects, such as oedema and haemorrhages (ARIA-E and -H), which are potentially linked to the induced immune response. To improve therapeutic safety, it is therefore imperative to understand the effects of anti-Aβ antibody treatment on immune cell function. We investigated the effects of long-term chronic Aducanumab treatment on amyloid plaque pathology and microglial response in the APP-SAA triple knock-in mouse model. Mice were treated weekly with Aducanumab from 4-8 months of age. Long-term treatment with Aducanumab results in a robust and dose-dependent removal of amyloid plaque pathology. Analysis of the CSF proteome indicates a reduction of markers for neurodegeneration including tau and α-synuclein. Consistent with a reduction of glucose uptake, the therapeutic effects were accompanied by reduced microglial activation. RNAseq confirmed a dose-dependent decrease in the disease-associated microglia (DAM) transcriptional signature of microglia, which is supported by a parallel decrease of Trem2 protein. However, genes associated with antigen-presentation were still increased after treatment. IHC confirms that Aducanumab treatment increases microglial clustering, as well as MHC-II expression around plaques and ELISA confirmed increased cytokine levels. These findings demonstrate that long-term chronic Aducanumab-mediated removal of Aβ leads to a dose dependent decrease in microglial activation and neurodegeneration, but induces a unique antibody treatment-related microglial phenotype associated with antigen presentation, which may be related to plaques still present after the 4 months treatment period.
000282944 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000282944 7001_ $$0P:(DE-HGF)0$$aSandmann, T.$$b1
000282944 7001_ $$0P:(DE-HGF)0$$aHa, C.$$b2
000282944 7001_ $$0P:(DE-HGF)0$$aXia, D.$$b3
000282944 7001_ $$0P:(DE-HGF)0$$aLewcock, JW$$b4
000282944 7001_ $$0P:(DE-HGF)0$$aMonroe, KM$$b5
000282944 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b6$$udzne
000282944 7870_ $$0DZNE-2025-00965$$ade Weerd, Lis et.al.$$dLondon : Biomed Central, 2025$$iRelatedTo$$r$$tEarly intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques.
000282944 8564_ $$uhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi
000282944 909CO $$ooai:pub.dzne.de:282944$$pVDB
000282944 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001304$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000282944 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2202037$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b6$$kDZNE
000282944 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000282944 9141_ $$y2025
000282944 9201_ $$0I:(DE-2719)1110007$$kAG Haass$$lMolecular Neurodegeneration$$x0
000282944 980__ $$adataset
000282944 980__ $$aVDB
000282944 980__ $$aI:(DE-2719)1110007
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