Hereditary Alzheimer's disease (hAD) and PSEN2 variants are rare, and the benefit of anti-amyloid β-directed monoclonal antibody (mAb) therapy is unknown. We encountered a 51-year-old Japanese woman with PSEN2 -associated hAD. A molecular diagnosis revealed a novel uniallelic missense variant (NM₀00447: c. 356T > G, p. Leu119Arg) in PSEN2. Intravenous mAb therapy was initiated at age 50, and serial amyloid positron emission tomography showed intense Pittsburgh compound B accumulation and a reduction in amyloid-β deposits in the cerebral cortex after 6 months. Our results suggest that treatment with mAbs has the potential to reduce amyloid deposits in the brain, even in patients with symptomatic hAD.
Kasuga et al. (Sun,) studied this question.