A novel PSEN2 missense variant in a Japanese woman with hereditary Alzheimer's disease

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 (NM_000447: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.