作为脑脊液中淀粉样蛋白水平生物标志物的klotho蛋白
-klotho as a biomarker of amyloid levels in the cerebrospinal fluid.
作者信息
Raber Jacob, Pederson Alexandra, Bunnell Emily, Mattek Nora, Gray Nora E, Kohama Steven G, Weiss Alison R, Quinn Joseph F, Urbanski Henryk F
机构信息
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States.
Department of Neurology, Oregon Health and Science University, Portland, OR, United States.
出版信息
Front Aging Neurosci. 2025 Jun 23;17:1599402. doi: 10.3389/fnagi.2025.1599402. eCollection 2025.
INTRODUCTION
CSF -klotho levels might affect Aβ40, Aβ42, and the Aβ42/40 ratio in the cerebrospinal fluid (CSF).
METHODS
CSF -klotho was assayed in ovariectomized rhesus macaques (NHPs) maintained on a Western-style diet (WSD) to assess the effect of estrogen hormone therapy (HT). CSF and serum -klotho was also analyzed in females and males of different ages and whether it was associated with Aβ42, Aβ40, or the Aβ42/40 ratio. Furthermore, CSF and serum -klotho were analyzed in women and men with dementia and controls and whether they were associated with CSF Aβ levels.
RESULTS
HT was associated with increased CSF -klotho levels. Furthermore, -klotho and Aβ levels were correlated in a species- and cognitive health-dependent fashion. Higher CSF and serum levels of -klotho were seen in controls than in patients with dementia.
DISCUSSION
Understanding the species differences in the beneficial effects of -klotho on CSF Aβ physiology should open new avenues for treating AD.
引言
脑脊液中β-klotho水平可能会影响脑脊液中Aβ40、Aβ42以及Aβ42/40比值。
方法
对采用西式饮食（WSD）喂养的去卵巢恒河猴（非人灵长类动物，NHPs）检测脑脊液β-klotho水平，以评估雌激素激素疗法（HT）的效果。还对不同年龄的雌性和雄性动物的脑脊液及血清β-klotho进行分析，以及其是否与Aβ42、Aβ40或Aβ42/40比值相关。此外，对患有痴呆症的女性和男性及其对照者的脑脊液和血清β-klotho进行分析，以及它们是否与脑脊液Aβ水平相关。
结果
激素疗法与脑脊液β-klotho水平升高有关。此外，β-klotho与Aβ水平以物种和认知健康依赖的方式相关。对照者的脑脊液和血清β-klotho水平高于痴呆症患者。
讨论
了解β-klotho对脑脊液Aβ生理学有益作用的物种差异应为治疗阿尔茨海默病开辟新途径。
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