Blood-based biomarkers for Alzheimer’s disease: influence of kidney function

Background Blood biomarkers may aid Alzheimer’s disease (AD) diagnosis; however, their reliability can be affected by systemic conditions such as kidney dysfunction (KD). We evaluated the impact of KD on plasma levels of amyloid-β (Aβ42/Aβ40), phosphorylated tau (p-Tau181, p-Tau217), and neurofilament light chain (NfL), and developed correction strategies. Methods We retrospectively selected 112 individuals (52 with AD, 21 with other neurodegenerative diseases, and 39 with non-neurodegenerative conditions) who had a previously documented abnormal renal function value. Participants were included based on the availability of: i)previously measured cerebrospinal fluid (CSF) Aβ42/Aβ40, p-Tau181, and NfL; ii) plasma samples for the measurement of Aβ42/Aβ40, p-Tau217, p-Tau181, and NfL; iii) paired serum samples collected at the same time to re-measure creatinine and ensure temporal correspondence between kidney function and biomarker assessments. Plasma biomarkers were quantified using the Lumipulse G1200 platform. Kidney dysfunction (KD) was defined as eGFR < 60 mL/min/1.73 m². Correction models were developed using linear regression and ROC curve analyses. Results KD was present in 51.8% of patients and associated with increased plasma levels of Aβ42, Aβ40, p-Tau181, p-Tau217, and NfL, not with the Aβ42/Aβ40 ratio. Creatinine-based correction improved the correlation between plasma and CSF NfL and enhanced the diagnostic performance of plasma p-Tau181 and p-Tau217 for AD. Corrected cut-offs aligned with those from KD-free cohorts. Conclusions KD alters plasma biomarker concentrations. Creatinine-based normalization in patients with KD may allow to rely on cut-offs generated on cohorts without KD. Funding: Italian Ministry of Health; Italian Research Association on Alzheimer’s Disease (AirAlzh); Parkinson’s Foundation.