Anti-amyloid β-peptide (Aβ) immunotherapy was developed as treatment for Alzheimer’s disease to reduce and prevent amyloid plaque pathology and its downstream consequences. Efficient amyloid plaque clearance has been proven in clinical trials with Aducanumab, Lecanemab and Donanemab. At least two of these antibodies slow memory decline to some extent and have beneficial effects on daily living activities. The therapeutic effects correlate with the efficacy of plaque removal. However, treatment is associated with adverse side-effects, such as oedema and haemorrhages, which are potentially linked to the induced immune response. To improve therapeutic safety, it is therefore imperative to understand the consequences of anti-Aβ antibody treatment on immune cell function. Here, 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, with a higher efficiency for removing diffuse over dense-core plaques. Analysis of the CSF proteome indicates a reduction of markers for neurodegeneration including Tau and α-Synuclein, as well as immune cell related proteins.