HAI Book 2025 - Flipbook - Page 570
Silva-Rodríguez, Jesús
129
Long-term cognitive and biomarker trajectories of cognitively
unimpaired individuals with elevated plasma ptau-217
Jesús Silva-Rodríguez1, Linda Zhang1, Elizabeth L. Valeriano-Lorenzo1, Francisco J. LópezGonzález1, Sonia Wagner-Reguero1, Teodoro del Ser1, Michel J. Grothe1, Pascual SánchezJuan1
1
Reina Sofia Alzheimer Centre, CIEN Foundation, ISCIII, Madrid, ES
Introduction: Plasma ptau-217 has demonstrated excellent performance in detecting AD pathology and in
distinguishing between AD and non-AD neurodegenerative disorders. However, its value for predicting long-term
cognitive decline among cognitively unimpaired (CU) individuals remains unclear.
Methods: We analyzed data from 1044 CU older individuals (75±4yrs, 64% female) enrolled in the Vallecas Project
at the CIEN Foundation (Madrid, Spain). Participants underwent annual assessments from 2011 to 2024, including
blood sampling, detailed clinical and neuropsychological evaluations, and MRI scanning (average follow-up:
7.2±3.0yrs). Baseline plasma ptau-217 levels were measured using the LUMIPULSE platform (Fujirebio). Subjects
were categorized as having either normal (ptau-) or elevated (ptau+) ptau-217 based on a pre-established
threshold of 0.247pg/mL. We used linear mixed-effects models to assess longitudinal group differences across
three key outcomes: a) cognitive performance, assessed using a modified preclinical Alzheimer9s cognitive
composite score (mPACC5); b) hippocampal volume, measured on serial MRI using SPM12/CAT12; and c) a blood
biomarker of astrocytic activation (GFAP, Simoa® platform, n=506). Additionally, Cox survival analysis was
performed to assess the risk of progressing to MCI or dementia. All models were adjusted for sex, baseline age,
and APOE4 status.
Results: 16.6% of the participants were classified as ptau+. These individuals showed significantly lower baseline
mPACC5 scores (z-score difference: -0.5, p
