Moreover, we combined antibody treatment with chronic BACE1 inhibitor treatment and demonstrate significant clearance of pre-existing amyloid deposits in transgenic mouse brain, without induction of microhemorrhages and other histopathological findings. Here, we describe the preclinical characterization of this antibody, and demonstrate a significant reduction in amyloid burden in the absence of microhemorrhages in different mouse models with established plaque deposition. We have developed a novel, high affinity antibody against AОІ peptides bearing a pyroglutamate residue at amino acid position 3 (3pE), an AОІ species abundantly present in plaque deposits in AD brains. Investigational disease-modifying approaches aiming at reducing cerebral AОІ concentrations include prevention of de novo production of AОІ through inhibition of ОІ-site amyloid precursor protein cleaving enzyme 1 (BACE1), and clearance of AОІ deposits via passive AОІ immunotherapy. Therefore, AОІ is strongly positioned as a promising and extensively validated therapeutic target for AD.

The imbalance between production and clearance of amyloid ОІ (AОІ) peptides and their resulting accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD).

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