Alzheimer's disease cerebrospinal fluid biomarkers and kidney function in normal and cognitively impaired older adults

I. Hajjar, Reem Neal, Zhiyi Yang, James Lah
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Abstract

Abstract INTRODUCTION Recent Alzheimer's disease (AD) clinical trials have used cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests that AD risk is related to impaired renal function. The impact of kidney function on commonly used AD biomarkers remains unknown. METHODS Participants in studies conducted at the Goizueta Alzheimer's Disease Research Center (N = 973) had measurements of serum creatinine and CSF AD biomarkers. General linear models and individual data were used to assess the relationships between biomarkers and eGFR. RESULTS Lower estimated glomerular filtration rate (eGFR) was associated with lower amyloid beta (Aβ)42/tau ratio (p < 0.0001) and Aβ42 (p = 0.002) and higher tau (p < 0.0001) and p‐tau (p = 0.0002). The impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (all p‐values were < 0.005). DISCUSSION The association between eGFR and CSF AD biomarkers has a significant impact that varies by cognitive status. Future studies exploring this impact on the pathogenesis of AD and related biomarkers are needed. Highlights There is a significant association between Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and both estimated glomerular filtration rate (eGFR) and mild cognitive impairment (MCI). Kidney function influences CSF biomarker levels in individuals with normal cognitive function and those with MCI. The impact of kidney function on AD biomarker levels is more pronounced in individuals with cognitive impairment. The variation in CSF tau levels is independent of cardiovascular factors and is likely directly related to kidney function. Tau may have a possible role in both kidney and cognitive function.
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正常和认知障碍老年人的阿尔茨海默病脑脊液生物标志物和肾功能
摘要 引言 最近的阿尔茨海默病(AD)临床试验使用脑脊液(CSF)生物标志物水平进行筛查和入组。初步证据表明,阿尔茨海默病风险与肾功能受损有关。肾功能对常用的 AD 生物标志物的影响尚不清楚。方法 戈伊祖塔阿尔茨海默病研究中心(Goizueta Alzheimer's Disease Research Center)的研究参与者(N = 973)测量了血清肌酐和脑脊液 AD 生物标志物。一般线性模型和个体数据用于评估生物标志物与 eGFR 之间的关系。结果 肾小球滤过率(eGFR)越低,淀粉样β(Aβ)42/tau比值(p < 0.0001)和Aβ42(p = 0.002)越低,tau(p < 0.0001)和p-tau(p = 0.0002)越高。eGFR对AD生物标志物水平的影响在认知障碍患者中更为明显(所有p值均小于0.005)。讨论 eGFR 与脑脊液 AD 生物标志物之间的关联具有显著影响,且因认知状况而异。今后需要开展研究,探讨这种关系对 AD 发病机制和相关生物标志物的影响。要点 阿尔茨海默病(AD)脑脊液(CSF)生物标志物与估计肾小球滤过率(eGFR)和轻度认知障碍(MCI)之间存在明显的关联。肾功能会影响认知功能正常者和 MCI 患者的 CSF 生物标志物水平。肾功能对注意力缺失症生物标志物水平的影响在认知障碍患者中更为明显。CSF tau水平的变化与心血管因素无关,可能与肾功能直接相关。Tau可能对肾脏和认知功能都有影响。
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