Work

Lecanemab in symptomatic PSEN1 p.Met233Val early‐onset Alzheimer's disease: Neuroimaging safety, regional amyloid‐PET dynamics, and longitudinal plasma biomarkers

Year: 2026

Type: article

Abstract: Introduction: .Met233Val variant is a Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU)-eligible autosomal-dominant Alzheimer's disease (ADAD) variant for which lecanemab response data are unavailable. Methods: .Met233Val carrier (APOE ε3/ε3) was prospectively followed through 26 lecanemab infusions over 12 months, with serial magnetic resonance imaging (MRI), amyloid positron emission tomography (PET), and plasma biomarkers. Results: No amyloid-related imaging abnormalities occurred. Composite Centiloid increased modestly (+7.2), masking regional divergence: basal ganglia (-24.5) and medial temporal cortex (-22.1) declined, whereas posterior cortical regions accrued amyloid. Plasma amyloid beta (Aβ) 42/40 rose to 122% by T22, with concurrent decreases in phosphorylated tau at threonine 217 (p-tau217), p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Global Clinical Dementia Rating (CDR) score remained 0.5; caregiver reports noted improvements in spasticity, dystonia, and affective features. Discussion: .Met233Val ADAD carrier. These longitudinal neuroimaging and plasma biomarker findings may help inform interpretation of treatment responses in genetically defined ADAD.

Source: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring

DOI: 10.1002/dad2.70468