Dataset Information

Beneficial effect of ACI-24 vaccination on microglial phenotypes in an amyloidosis mouse model

ABSTRACT: Amyloid-beta (Aβ) deposition is an initiating factor in Alzheimer´s disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating phagocytic function. Immunotherapies are currently pursued as therapeutic strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated the effect of the Aβ targeting ACI-24 vaccine in preventing the AD pathology in an amyloidosis mouse model. ACI-24 vaccination elicited a robust and sustained antibody response in APPPS1 mice with an accompanying reduction of Aβ plaque load, amyloid plaque-associated ApoE and dystrophic neurites as compared to non-vaccinated controls. Furthermore, plaque-associated microglia had the tendency to be more activated post vaccination. The lower Aβ plaque load triggered by vaccination with ACI-24 was in concordance with the bulk transcriptomic analysis that revealed a reduction in the expression of several disease-associated microglial signatures. Accordingly, plaque-distant microglia displayed a more ramified morphology, supporting beneficial effects of the vaccination on bulk microglial phenotypes. Our study demonstrates that administration of the Aβ targeting vaccine, ACI-24, triggers protective microglial responses that translate into a reduction of AD pathology suggesting its use as a safe and cost effective AD therapeutic intervention.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Microglial Cell

DISEASE(S): Alzheimer's Disease

SUBMITTER: Stephan Mueller

LAB HEAD: Stefan F. Lichtenthaler

PROVIDER: PXD038665 | Pride | 2023-01-09

REPOSITORIES: Pride

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Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model.

Rudan Njavro Jasenka J Vukicevic Marija M Fiorini Emma E Dinkel Lina L Müller Stephan A SA Berghofer Anna A Bordier Chiara C Kozlov Stanislav S Halle Annett A Buschmann Katrin K Capell Anja A Giudici Camilla C Willem Michael M Feederle Regina R Lichtenthaler Stefan F SF Babolin Chiara C Montanari Paolo P Pfeifer Andrea A Kosco-Vilbois Marie M Tahirovic Sabina S

Cells 20221224 1

Amyloid-β (Aβ) deposition is an initiating factor in Alzheimer's disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ plaques, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating the phagocytic function of immune cells. Immunotherapies are currently pursued as strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. He ...[more]

PMID: 36611872

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