Abstract
BACKGROUND AND OBJECTIVES: Interest in plasma biomarkers for neurodegenerative disorders is growing, but their reliance on glomerular filtration makes kidney function a key potential confounder. This study assesses the effect of kidney function (eGFR) on plasma biomarkers of neurodegeneration and on their accuracy for detecting cerebral amyloidosis. METHODS: This observational study aims at studying the effect of kidney function on blood biomarkers through simultaneous measurements of creatinine, plasma, and CSF biomarkers (Aβ42, Aβ40, p-tau181, p-tau217, neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], and brain-derived tau [BD-tau]), as well as plasma biomarker ratios (Aβ42/Aβ40, p-tau217/Aβ42, NfL/p-tau217, and p-tau181/Aβ42), in the ALZAN cohort of patients. This prospective multicenter cohort (#NCT05427448), recruited across Montpellier, Nîmes, and Perpignan hospitals, included patients from November 2022 to July 2024 who met the following criteria: age ≥18 years, informed consent, and concomitant CSF and blood sampling. To determine the association between plasma biomarkers and kidney function, we performed univariable linear regression analyses. RESULTS: A total of 420 patients were included (mean age: 71.1 years, %female: 53.2) and subdivided into 3 groups according to eGFR value (ml/minute/1.73 m(2)): <60 (n = 36), [60-90] (n = 194), and >90 (n = 190). All mean plasma biomarker levels were significantly higher in the eGFR < 60 group. Except for p-tau217, a statistically significant inverse correlation was observed between eGFR and individual plasma biomarkers. Furthermore, age-adjusted univariable linear regression analysis revealed an association between eGFR and all plasma biomarkers. Kidney dysfunction significantly impaired the specificity of several biomarkers (p-tau181, GFAP, NfL, and BD-tau; p < 0.001) for detecting cerebral amyloidosis (CSF Aβ42/Aβ40 < 7%), whereas p-tau217 was unaffected. It is important to note that ratio-based plasma biomarkers were not influenced by reduced kidney function. DISCUSSION: Impaired kidney function was linked to increased plasma cerebral amyloidosis biomarkers, but ratio-based measures (especially p-tau217/Aβ42) showed stable sensitivity and specificity for detecting cerebral amyloidosis across all eGFR groups. Additional studies including more patients with lower eGFR values in diverse diagnostic settings are needed to clarify the influence of kidney function on these biomarkers. CLASSIFICATION OF EVIDENCE: This Class II evidence shows that kidney function influences individual blood biomarkers used for cerebral amyloidosis detection, but not their ratios. TRIAL REGISTRATION INFORMATION: NCT05427448.