Abstract Body

Background:

The Longitudinal Early-onset Alzheimer’s Disease study (LEADS) recruits early-onset Alzheimer’s Disease (EOAD), amyloid-negative cognitively impaired (EOnonAD), and age-matched controls (CN) participants – with enrollment ongoing.

Methods:

LEADS’s goal is to recruit 400 EOAD, 200 EOnonAD, and 100 CN. LEADS participants undergo cognitive, MRI, amyloid- and tau-PET, and plasma biomarker assessments annually. Cognitive trajectories were examined using mixed-effects modeling controlling for age, sex, and education. PET SUVR were calculated based on optimized composited reference regions. MRI and PET changes over time were determined using linear mixed effect models with random intercepts and slopes. Plasma biomarkers (Ab 42/40, GFAP, NfL) were measured at the University of Gothenburg, Sweden using Quanterix N4PE assay.

Results:

Significantly greater slopes of decline were seen across global cognition, attention, and visuospatial skills (ps<.05) at 12 months, with further decline in verbal memory, language, and executive skills at 24 months for EOAD (n=127 at 12, n=42 at 24 months) than CN (n=71 at 12, n=38 at 24 months). Longitudinal T1 MRI (n=111 EOAD) demonstrated a 2-4% annualized atrophy rate in AD-signature cortical regions, greatest in inferior parietal and posterolateral temporal cortices. Smaller effects were present in entorhinal and hippocampal regions. Florbetaben centiloid values (n=120 EOAD) increased over time by 4.4 CL/year (95%CI [3.5, 5.3], p<.001). Temporal Flortaucipir SUVR (n=111 EOAD) increased by 0.019 SUVR/year (95%CI [0.009, 0.028], p<.001). Plasma biomarkers (Ab 42/40, GFAP, NfL) correlated with one another and were associated with EOAD showing similar findings relative to published literature.

Conclusions:

This is the first report of baseline plasma biomarkers and annualized changes in cognition, atrophy, amyloid-, and tau-accumulation in EOAD participants from LEADS. Future work will include examining differential rates of change between EOAD and LOAD.