Associations of Blood and Cerebrospinal Fluid Aβ and tau Levels with Renal Function

Sun, Hao‐Lun; Yao, Xiu-Qing; Li, Lei; Jin, Wang-Sheng; Bai, Yang; Zeng, Guihua; Shi, An-Yu; Liang, Jun; Zhu, Liangru; Liu, Yuhui; Wang, Yanjiang; Bu, Xian‐Le

doi:10.1007/s12035-023-03420-w

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Syrjanen et al found that CKD was associated with higher plasma Aβ40, Aβ42, total-tau, and NfL levels [ 11 ]. Sun et al reported plasma levels of Aβ40, Aβ42, and total-tau were positively associated with the medical history of CKD and negatively associated with eGFR [ 14 ]. An investigation by Adam et al revealed that less than 10% of CKD patients were aware of their disease [ 38 ] because CKD remained asymptomatic until the late stage [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous literature has reported associations between medical comorbidities and AD plasma biomarkers. Several studies suggested that renal function indicators and medical history of CKD were associated with higher plasma total-tau, Aβ40, Aβ42 [ 14 , 15 ], NfL [ 16 – 18 ], and P-tau181 levels [ 18 – 22 ]. However, a significant portion of the previous studies were hospital-based [ 14 , 20 ], not including the Asian population, or lacked the data of glomerular filtration rate (GFR), a precise measure of kidney function [ 19 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies suggested that renal function indicators and medical history of CKD were associated with higher plasma total-tau, Aβ40, Aβ42 [ 14 , 15 ], NfL [ 16 – 18 ], and P-tau181 levels [ 18 – 22 ]. However, a significant portion of the previous studies were hospital-based [ 14 , 20 ], not including the Asian population, or lacked the data of glomerular filtration rate (GFR), a precise measure of kidney function [ 19 , 23 ]. An Asian population-based study with objective assays, comprehensively examining the association between GFR and plasma AD markers, is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Wu,

Xiao,

Wang

et al. 2024

Alz Res Therapy

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Background The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. Methods Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. Results The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = − 0.19, 95% CI − 0.224 to − 0.156, P < 0.001; B = − 0.009, 95% CI − 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = − 0.010, 95% CI − 0.133 to − 0.068, P < 0.001), but not with P-tau181 (B = − 0.003, 95% CI − 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = − 0.790, 95% CI − 1.026 to − 0,554, P < 0.001). Conclusions Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Wu,

Xiao,

Wang

et al. 2024

Alz Res Therapy

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“…Although the importance of blood pressure, dyslipidemia (DLP), and diabetes mellitus (DM) has been studied, the most frequently reported factor is renal function. Thus, individuals with chronic renal failure have been shown to have higher levels of plasma Aβ and p-tau than those of healthy individuals [10,11]. However, these studies have been mainly performed by measuring plasma biomarkers with SIMOA (single-molecule array) or ELISA (enzyme-linked immunosorbent assay) technologies, and there is very little information about automatic immunoassays, such as Lumipulse, a promising and widely available technique that allows the measurement of AD markers in a fully automated way.…”

Section: Introductionmentioning

confidence: 99%

Influence of Physiological Variables and Comorbidities on Plasma Aβ40, Aβ42, and p-tau181 Levels in Cognitively Unimpaired Individuals

Martínez-Dubarbie,

Guerra-Ruiz,

López-García

et al. 2024

IJMS

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Plasma biomarkers for Alzheimer’s disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.

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“…13 It has also been suggested that the risk of Alzheimer's disease is related to impaired renal function and its impact on levels of AD biomarkers in the plasma. 14,15 Since the CSF is a highly controlled microenvironment, studying the association of kidney function with CSF biomarkers offers great insight into the kidney-brain axis. 12,16 In this study, we aimed to investigate the association between estimated glomerular filtration rate (eGFR), as a measure of kidney function, and the levels of AD biomarkers in the CSF-specifically, the Aβ42/Tau ratio and individual other individual AD biomarkers: Amyloid beta 1-42 (Aβ42), Tau, and phosphorylated Tau181 (pTau)-in individuals with and without cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults

Hajjar,

Neal,

Yang

et al. 2023

Preprint

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ImportanceRecent Alzheimer’s disease (AD) clinical trials have used Cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests Alzheimer’s Disease (AD) risk may be related to impaired renal function but the association of variation in levels of commonly used AD biomarkers with kidney function are unknown.ObjectiveTo investigate the association between estimated glomerular filtration rate (eGFR), CSF levels of AD biomarkers: amyloid beta1–42 (Aβ42), Tau or phosphorylated Tau181 (pTau).Design, Setting, and ParticipantsWe conducted an analysis using data from participants enrolled in two research protocols at the Goizueta Alzheimer’s Disease Research Center that had simultaneous measurements of serum creatinine at the time of their Cerebrospinal fluid (CSF) collection (N=973). The participants had a mean age of 66.52 years, 23.33% were African American, and 63% were women, with 42.46% having mild cognitive impairment (MCI). The estimated glomerular filtration rate (eGFR) was obtained from chronic kidney disease Epidemiology Collaboration. All participants had similar CSF collection procedures. Aβ42, Tau or pTau were measured on the Luminex ALZBIO platform. General linear models and individual data were used to assess relationships between biomarkers and eGFR.ResultsLower eGFR was associated with lower Aβ42/Tau ratio (slope= 0.033 units, p<0.0001) and Aβ42 (slope=0.75, p=0.002) and higher Tau (slope= -0.39, p<0.0001) and pTau (slope= -0.13, p=0.0002). Although these associations remained significant after adjusting for cognitive status, we observed interactions between MCI and eGFR. This interaction revealed that the impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (interaction MCI*GFR p-values were 0.005 for Ab42, 0.04 for tau and pTau, and 0.05 for the ratio).ConclusionWe found a significant association between eGFR with CSF AD-biomarkers that may differ by cognitive status. This suggests that kidney function should be considered both in the context of interpreting AD biomarkers as well as exploring potential systemic factors that may increase risk of AD. Future longitudinal studies need to further explore the impact of kidney function on the pathogenesis of AD and related Biomarkers.KEY POINTSQuestionAre Cerebrospinal Fluid (CSF)AD-biomarker measurements impacted by kidney function?FindingsIn this analysis of data from 973 individuals who had both cerebrospinal fluid (CSF) AD-biomarkers (Aβ42, Tau, and pTau181) and kidney function measurements, there were significant associations between estimated glomerular filtration rate (eGFR) and measures of CSF AD-biomarkers. These associations were more pronounced in those with cognitive impairment.MeaningKidney function may have a significant impact on AD-biomarker measurements in the CSF, especially in those in the early symptomatic stages of AD.

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Associations of Blood and Cerebrospinal Fluid Aβ and tau Levels with Renal Function

Cited by 5 publications

References 43 publications

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Influence of Physiological Variables and Comorbidities on Plasma Aβ40, Aβ42, and p-tau181 Levels in Cognitively Unimpaired Individuals

Alzheimer’s Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults

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