HAI Book 2025 - Flipbook - Page 578
Cody, Karly
133
Effects of amyloid and tau status on multiplex plasma CNS and
inflammatory proteins in a normal aging cohort
Alexandra N Trelle1, Karly A Cody1, Tran T Nguyen2, Joseph R Winer1, Skylar Weiss1, America
Romero1, Isha Sai1, Edward N Wilson1,3, Anthony D Wagner3,4, Holden T Maecker3,5, Elizabeth C
Mormino1,3
1
Neurology & Neurological Sciences, Stanford School of Medicine, Stanford, CA, US
Institute for Immunity, Transplantation, and Infection Operations, Stanford University, Stanford, CA, US
3
Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, US
4
Psychology, Stanford University, Stanford, CA, US
5
Microbiology and Immunology, Stanford University, Stanford, CA, US
2
Objective: Scalable plasma markers are needed to capture canonical Alzheimer9s disease biomarkers, as well as
additional biological pathways relevant for cognitive decline in human aging.
Methods: We evaluated plasma CNS and inflammatory proteins from newly developed multiplex panels (NULISA,
Alamar) in clinically unimpaired individuals from the Stanford Aging and Memory Study with available Lumipulse
CSF A´42/A´40 and pTau181 data (n=132; mean (SD) age = 68.8 (5.6) years; 78 female). Cross-sectional fold change
differences by A-status (CSF A´42/A´40
50.61) were examined using Wilcoxon
rank-sum tests (FDR-corrected, p=0.005) across NULISA targets (125 CNS proteins; 250 inflammatory proteins).
Spearman correlations assessed continuous associations between NULISA pTau isoforms and CSF proteins. ROC
curves evaluated discriminative accuracy of NULISA A´ and pTau isoforms for amyloid and tau positivity. Linear
mixed models assessed change over time of selected NULISA targets in individuals with longitudinal follow-up
(n=49; mean (SD) follow-up 5.6 (1.9) years).
Results: Significant differences between A+ and A- individuals were observed for pTau217, pTau231, pTau181,
A´42, and GFAP (Figure 1A). Significant differences between T+ and T- individuals were observed for CNS panel
targets pTau217, pTau231, pTau181, GFAP, TIMP3, SAA1, and inflammatory panel targets TIMP1, CSF3, TREM1,
CXCL11, THPO, LGALS9, S100A12 (Figure 1B). Moderate correlations were observed between NULISA pTau
isoforms and CSF A´42/A´40 and pTau181 (Figure 2). NULISA pTau isoforms exhibited high discriminative
accuracy for predicting CSF A and T status (Table 1). Among NULISA targets that differed between A or T groups,
pTau217, pTau231, and CSF3 exhibited significant increases and Ab42 exhibited significant decreases over time
(p
