Abstract
<jats:p>Amyloid plaques, one of the defining features of Alzheimer's disease, are associated with synapse loss and accumulation of pathological tau in dystrophic neurites and reactive glia in their immediate vicinity. Anti-amyloid-beta; immunotherapies have been shown to effectively remove a large proportion of plaques from the brain, but whether immunotherapies reduce pathological changes around remaining plaques or plaques that emerge after treatment remains unknown. We examined amyloid plaques, synapses, astrocytes, and phosphorylated tau in post-mortem brain tissue from people with Alzheimer's disease who received Amyloid-beta42 immunization in the AN1792 trial (Elan Pharmaceuticals), non-immunized or placebo-treated people with Alzheimer's disease, and neurologically healthy controls. In non-vaccinated individuals, we observe plaque-associated synapse loss, phospho-tau accumulation, and astrogliosis as previously reported. People who received Amyloid-beta42 vaccination had reduced pathology up to 14 years after receiving the vaccine including ameliorated plaque-associated synapse loss, less accumulation of phospho-tau around plaques (AT8 and pTau217), lower levels of astrogliosis, and lower levels of phospho-tau associated with synapses. These data indicate that anti-amyloid active vaccines may have lasting beneficial effects even around remaining plaques or plaques formed after immunization.</jats:p>