Aβ Antibodies Target Not Only Amyloid Plaques But Also Distinct Brain Cells And Vessels
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Background
Antibodies against amyloid-β (Aβ) are the only therapies capable of slowing cognitive decline and reducing Aβ plaque burden in Alzheimer’s disease (AD). Yet the precise sites where antibodies engage Aβ in the brain, and the mechanisms that drive Aβ clearance, are not fully defined. Defining the Aβ antibody engagement with Aβ in brain is essential to understand how immunotherapy can be beneficial for AD.
Methods
We administered the well-establsihed N-terminal Aβ antibody 6E10 via intrahippocampal (IH), cisterna magna (CM), or intraperitoneal (IP) injection in AD mouse models. N-terminal Aβ antibodies were seen as most effective in AD mouse models. Antibody 6E10 was not only assessed in Aβ plaques, but also examined in association with diverse brain cells and vascular compartments. Glymphatic dynamics were evaluated following Aβ antibody treatment.
Results
As expected, Aβ antibody 6E10 bound to Aβ plaques but remarkably also localized to vulnerable neurons, such as hippocampal CA1 pyramidal cells, as well as microglia, astrocytes, oligodendrocytes, perivascular macrophages (PVMs), and blood vessels. Glymphatic function showed no significant alterations after antibody administration.
Conclusions
Aβ antibodies distribute not only to amyloid plaques but also to neurons, glial cells, and blood vessels. This study provides detailed localizations of antibody in the AD brain, offering valuable insights into cellular targets and spatial dynamics of Aβ antibody-based immunotherapy.
