journal articles
ASSOCIATIONS OF PLASMA BIOMARKERS WITH AGE IN THE PRESENILIN-1 E280A AUTOSOMAL DOMINANT ALZHEIMER\'S DISEASE KINDRED
Vincent Malotaux, Vivian Ku, Paula Ospina Lopera, Yi Su, Yinghua Chen, Alpana Singh, Jonathan Ruiz-Triviño, María José Hidalgo, Laura Osorio, Laura Serna, Daniela Giraldo, Diana Alzate, Bing He, Catarina Tristão-Pereira, Liliana Ramirez Gomez, Sonia Do Carmo, A. Claudio Cuello, Nicholas J. Ashton, Eric M. Reiman, David Aguillón, Yakeel T. Quiroz
BACKGROUND: Autosomal-dominant Alzheimer’s disease (ADAD) offers a model to define early biological changes in Alzheimer’s disease due to its predictable age at symptom onset. Although ultrasensitive plasma assays are available, their associations with age in ADAD remain incompletely characterized.
OBJECTIVES: To characterize age-related changes in plasma biomarkers and examine associations with cognition in PSEN1 E280A ADAD.
DESIGN AND SETTING: Cross-sectional observational study in members of the Colombian PSEN1 E280A kindred.
PARTICIPANTS: A total of 164 individuals were included, comprising 83 mutation carriers (mean age 34.36±9.82 years; 54% female) and 81 non-carriers (mean age 33.75±9.84 years; 52% female).
MEASUREMENTS: Plasma Aβ42/Aβ40, phospho-tau217 (p-tau217), brain-derived tau (BD-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were quantified. Sex-adjusted associations with age, divergence ages between groups, classification performance (ROC curves), and associations with cognition (MMSE and CERAD delayed recall) were assessed.
RESULT: All plasma biomarkers were associated with age (p < .01). Divergence between carriers and non-carriers began with Aβ42/Aβ40 before age 18, followed by p-tau217 (26.0 years), GFAP (26.1 years), BD-tau (27.9 years), and NfL (38.7 years). Aβ42/Aβ40 showed the highest discrimination of mutation status (AUC=0.99), followed by p-tau217 (AUC=0.87) and GFAP (AUC=0.84). Among carriers, p-tau217, GFAP, BD-tau, and NfL were associated with MMSE, while p-tau217, GFAP, and NfL predicted CERAD delayed recall.
CONCLUSION: Plasma biomarkers exhibit a temporal cascade in PSEN1 E280A ADAD. P-tau217 and GFAP show the strongest associations with early cognitive decline, suggesting their potential utility for tracking disease progression and monitoring treatment effects in E280A carriers.
CITATION:
Vincent Malotaux ; Vivian Ku ; Paula Ospina Lopera ; Yi Su ; Yinghua Chen ; Alpana Singh ; Jonathan Ruiz-Triviño ; María José Hidalgo ; Laura Osorio ; Laura Serna ; Daniela Giraldo ; Diana Alzate ; Bing He ; Catarina Tristão-Pereira ; Liliana Ramirez Gomez ; Sonia Do Carmo ; A. Claudio Cuello ; Nicholas J. Ashton ; Eric M. Reiman ; David Aguillón ; Yakeel T. Quiroz (2025): Associations of plasma biomarkers with age in the presenilin-1 E280A autosomal dominant Alzheimer's disease kindred. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100578