In 541 cognitively unimpaired, late middle-aged Hispanic, non-Hispanic Black, and non-Hispanic White adults, brain-derived phosphorylated-tau 217 (BD-p-tau217), measured via NULISAseq multiplex plasma assay, emerged as the strongest plasma predictor of cerebral amyloid burden on 18F-Florbetaben PET (β = 0.22, p < 0.001). Plasma Aβ42, IGFBP7, and BACE1 were each negatively associated with amyloid load. Critically, moderate-to-severe chronic kidney disease (CKD) significantly attenuated the BD-p-tau217 signal (interaction β = −0.17, p < 0.001), suggesting kidney clearance confounds biomarker interpretation.
This finding carries real clinical weight. BD-p-tau217 has rapidly ascended as a leading blood-based Alzheimer's screening candidate, but most validation work has occurred in highly selected, predominantly White clinical cohorts. Testing it in a racially and ethnically diverse community sample strengthens generalizability considerably. The kidney-function interaction is particularly actionable: CKD disproportionately affects older adults and minority populations—precisely the groups targeted for dementia screening—meaning plasma tau readings could be systematically misleading in a substantial subset of patients. Clinicians using these panels should obtain concurrent kidney function estimates and interpret tau biomarkers cautiously when eGFR falls below 60 mL/min/1.73 m².
Limitations include the cross-sectional design, which cannot establish causality or predict conversion to dementia. The IGFBP7 and BACE1 associations are exploratory and require replication. As a preprint posted to medRxiv and not yet peer-reviewed, these findings should be considered preliminary—full peer scrutiny may refine or revise the conclusions.
