AI Summary
In this study, researchers analyzed the γ-secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease using data from the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). The findings indicate that the clinical variability in individuals with this disease may be influenced by the effects of PSEN1 variants on γ-secretase activity and amyloid β production. This research supports targeting γ-secretase as a potential therapeutic strategy and suggests that cell-based models could help predict symptom onset.
Our findings suggest that clinical heterogeneity in people with autosomal dominant Alzheimer’s disease can be at least partly explained by different effects of PSEN1 variants on γ-secretase activity and amyloid β production. They support targeting γ-secretase as a therapeutic approach and suggest that cell-based models could be used to improve prediction of symptom onset.