Mitigating the Associations of Kidney Dysfunction With Blood Biomarkers of Alzheimer Disease by Using Phosphorylated Tau to Total Tau Ratios.
Mitigating the Associations of Kidney Dysfunction With Blood Biomarkers of Alzheimer Disease by Using Phosphorylated Tau to Total Tau Ratios.
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通过磷酸化Tau蛋白与总Tau蛋白的比值减轻肾功能障碍与阿尔茨海默病血液生物标志物的关联
DOI：
10.1001/jamaneurol.2023.0199
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发表时间：
2023-05-01
期刊：
影响因子：
29
通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
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作者：
Janelidze, Shorena;Barthelemy, Nicolas R.;He, Yingxin;Bateman, Randall J.;Hansson, Oskar
This cross-sectional study investigates associations of chronic kidney disease with plasma ratios of phosphorylated tau 217 and 181 to the corresponding unphosphorylated peptides in Alzheimer disease. Is chronic kidney disease (CKD) associated with changes in plasma concentrations of phosphorylated tau biomarkers (ie, p-tau217 and p-tau181) and corresponding percent phosphorylated tau to unphosphorylated tau ratios (pT217/T217 and pT181/T181)? In this cross-sectional study including 473 participants from 2 independent cohorts, CKD was associated with increased plasma concentrations of p-tau217 and p-tau181. However, associations of CKD with the percent ratios and with pT217/T217 in particular were clearly attenuated. To mitigate the associations of comorbidities like CKD with the performance of plasma AD biomarkers, certain biomarker ratios and specifically pT217/T217 should be considered for implementation in clinical practice and drug trials. 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). To investigate associations of CKD with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in AD. 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. 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. Associations between plasma-soluble p-tau and CKD. 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. 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.
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DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
影响因子：
14
作者：
Binette, Alexa Pichet;Janelidze, Shorena;Cullen, Nicholas;Dage, Jeffrey L.;Bateman, Randall J.;Zetterberg, Henrik;Blennow, Kaj;Stomrud, Erik;Mattsson-Carlgren, Niklas;Hansson, Oskar
通讯作者：
Hansson, Oskar
影响因子：
29
作者：
Leuzy, Antoine;Smith, Ruben;Hansson, Oskar
通讯作者：
Hansson, Oskar
影响因子：
4
作者：
Hertze, Joakim;Minthon, Lennart;Hansson, Oskar
通讯作者：
Hansson, Oskar
DOI：
10.1186/s13195-022-01005-8
发表时间：
2022-05-14
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
通讯作者：
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