# Mitigating the Associations of Kidney Dysfunction With Blood Biomarkers of Alzheimer Disease by Using Phosphorylated Tau to Total Tau Ratios

Article · Janelidze S, Barthélemy NR, He Y, Bateman RJ, Hansson O

- Archive id: doi:10.1001/jamaneurol.2023.0199
- Published: 2023-05-01
- Venue: JAMA neurology
- DOI: https://doi.org/10.1001/jamaneurol.2023.0199
- PMID: 36987840
- PMCID: PMC10061310
- Citations: 165
- Source URL: https://doi.org/10.1001/jamaneurol.2023.0199
- PDF: https://europepmc.org/articles/PMC10061310/pdf
- Provenance: europepmc

## Abstract

Importance Chronic kidney disease (CKD) has been associated with increased plasma concentrations of phosphorylated tau (p-tau) 217 and p-tau181, which potentially decreases their usefulness in the diagnostic workup of Alzheimer disease (AD). Objective To investigate associations of CKD with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in AD. Design, setting, and participants This cross-sectional study included patients with mild cognitive impairment (cohort 1; enrollment in 2000-2005) and replication in cohort 2 from the Swedish BioFINDER-2 study, including both cognitively unimpaired individuals and those with cognitive impairment (enrollment in 2017-2022). All participants were from 2 memory clinics in Sweden and had plasma tau assessments and CKD status established within 6 months of plasma collection. Exposures P-tau217 and p-tau181, unphosphorylated peptides (Tau212-221 and Tau181-190), and the ratios (pT217/T217 and pT181/T181) as well as estimated glomerular filtration rate (eGFR) as an indicator of CKD. Main outcomes and measures Associations between plasma-soluble p-tau and CKD. Results A total of 141 participants from cohort 1 (mean \[SD\] age, 72.2 \[7.7\] years; 82 \[58.2%\] women) and 332 participants from cohort 2 (172 with cognitive impairment and 160 cognitively unimpaired individuals; mean \[SD\] age, 69.8 \[9.4\] years; 169 \[50.9%\] women) were included. Higher eGFR was associated with increased levels of plasma p-tau217, p-tau181, Tau212-221, and Tau181-190 in individuals with cognitive impairment (cohort 1: R range, -0.24 to -0.59; P \< .004; cohort 2: R range, -0.18 to -0.53; P \< .02) and cognitively unimpaired individuals (cohort 2: R range, -0.44 to -0.50; P \< .001). However, eGFR did not correlate with the pT217/T217 ratio in patients with cognitive impairment (cohort 1: R, -0.11; P = .19; cohort 2: R, -0.02; P = .78), and the correlations with pT217/T217 ratio were significantly attenuated in cognitively unimpaired individuals (difference: R, -0.14 \[95% CI, -0.22 to -0.007\]; P = .001). For p-tau217 and pT217/T217, the mean fold increases in amyloid-β positive (Aβ+) compared with Aβ- groups ranged from 2.31 (95% CI, 1.86-2.77) to 4.61 (95% CI, 3.39-5.83) in participants with cognitive impairment and from 1.26 (95% CI, 0.98-1.55) to 1.27 (95% CI, 0.94-1.59) in cognitively unimpaired individuals and were clearly higher than the mean fold increases in those with CKD compared with those without CKD, ranging from 0.05 (95% CI, -0.28 to 0.38) to 0.72 (95% CI, 0.25-1.19) in participants with cognitive impairment and from 0.09 (95% CI, -0.08 to 0.26) to 0.36 (95% CI, 0.19-0.52) in cognitively unimpaired individuals. Conclusions and relevance In this study, CKD was associated with increased plasma levels of soluble tau, but for p-tau217 the associations were considerably lower than the association with Aβ positivity. Importantly, the ratios, and especially pT217/T217, were less associated with CKD than p-tau forms alone and therefore are likely to more accurately reflect AD-related pathological changes.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Alzheimer's, Parkinson's & Neurodegeneration](https://space-kitty.com/topics/neurodegeneration)

Cited in dossiers:
- [Alzheimer's, Parkinson's & Neurodegeneration: State of the Field (October 2026)](https://space-kitty.com/dossiers/neurodegeneration)

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