INVESTIGATING THE MECHANISMS OF AMYLOID BETA (AΒ) CLEARANCE IN THE COURSE OF PASSIVE IMMUNOTHERAPIES IN ALZHEIMER’S DISEASE
Charité – Universitätsmedizin Berlin
Presentation
Date TBA
Event Information
Poster Board
PS03-08AM-118
Poster
View posterAbstract
Passive immunotherapy targeting amyloid beta (Aβ) has recently emerged as a break-through disease-modifying strategy in Alzheimer’s disease (AD). However, its clinical efficacy is still limited and a deeper understanding of the mechanisms underlying antibody-mediated Aβ clearance is needed to improve the treatment efficacy.
We aim to determine how microglia influence the outcome of anti-Aβ immunotherapy and how antibody treatment in both brain and periphery affects the AD-like pathology. Using the Aβ overexpressing APPPS1 transgenic mice model, we administer the murine version of anti-Aβ antibodies, at various stages of pathology and in the presence or absence of microglia.
Aβ pathology, neuroinflammation and markers of neurodegeneration are assessed using immunohistochemistry, confocal fluorescence microscopy and electrochemiluminescence. To uncover molecular mechanisms across central nervous system cell populations, we employ proteomics, which is validated by RT-qPCR and Western Blot analyses.
Our preliminary data indicate that removal of microglia indeed influences the effects of the anti-Aβ treatment, supporting a crucial effector role of these cells. This study provides mechanistic insight into current anti-Aβ therapies and offers potential strategies to optimize immunotherapy in AD.
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