背景:我们检查了衰老抑制基因KLOTHO的功能优势KL-VS变体(KL-VS杂合性[KL-VSHET])是否赋予了抵抗以脑脊液(CSF)为指标的衰老有害影响的弹性神经炎症生物标志物(白介素-6[IL-6],S100钙结合蛋白B[S100B],在骨髓细胞上表达的触发受体[sTREM2],几丁质酶-3-样蛋白1[YKL-40],胶质纤维酸性蛋白[GFAP]),神经变性(总α-突触核蛋白[α-Syn],神经丝轻链蛋白),和突触功能障碍(神经颗粒素[Ng])。
方法:这个阿尔茨海默病风险丰富的队列由454名认知未受损的成年人组成(Mage=61.5±7.75)。协变量调整的多元回归检查了年龄(平均分割[年龄≥62])和CSF生物标志物(Roche/NeuroToolKit)之间的关系,以及它们在KL-VSHET(N=122)和非载波(KL-VSNC;N=332)之间是否存在差异。
结果:年龄较大与所有分析物的生物标志物谱较差相关(Ps≤0.03)。在年龄分层分析中,KL-VSNC表现出相同的模式(Ps≤0.05),这对于IL-6,S100B,Ng,和KL-VSHET中的α-Syn(Ps≥0.13)。尽管GFAP的年龄相关差异,两组sTREM2和YKL-40均明显(Ps≤0.01),KL-VSNC的作用幅度明显更强。
结论:较高水平的神经炎症,神经变性,KL-VSHET减弱了老年人的突触功能障碍。
结论:年龄较大与所有脑脊液神经炎症生物标志物的分布较差相关,神经变性,和突触功能障碍.KLOTHOKL-VS非载波表现出相同的模式,白细胞介素-6,S100钙结合蛋白B的年轻和老年KL-VS杂合子之间没有显着差异,神经颗粒素,和总α-突触核蛋白。尽管胶质纤维酸性蛋白的年龄相关差异,在骨髓细胞上表达的触发受体,和几丁质酶-3样蛋白1在两个KL-VS组中都很明显,对于KL-VS非携带者,效果的幅度明显更强。更高水平的神经炎症,神经变性,老年人的突触功能障碍在KL-VS杂合子中减弱。
BACKGROUND: We examined whether the aging suppressor KLOTHO gene\'s functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin-6 [IL-6], S100 calcium-binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase-3-like protein 1 [YKL-40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α-synuclein [α-Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]).
METHODS: This Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate-adjusted multivariate regression examined relationships between age (mean-split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL-VSHET (N = 122) and non-carriers (KL-VSNC; N = 332).
RESULTS: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age-stratified analyses, KL-VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL-6, S100B, Ng, and α-Syn (Ps ≥ 0.13) in KL-VSHET. Although age-related differences in GFAP, sTREM2, and YKL-40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL-VSNC.
CONCLUSIONS: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL-VSHET.
CONCLUSIONS: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction. KLOTHO KL-VS non-carriers exhibit this same pattern, which is does not significantly differ between younger and older KL-VS heterozygotes for interleukin-6, S100 calcium-binding protein B, neurogranin, and total α-synuclein. Although age-related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase-3-like protein 1 are evident for both KL-VS groups, the magnitude of the effect is markedly stronger for KL-VS non-carriers. Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL-VS heterozygotes.