Dark Heather E, Paterson Clare, Daya Gulzar N, Peng Zhongsheng, Duggan Michael R, Bilgel Murat, An Yang, Moghekar Abhay, Davatzikos Christos, Resnick Susan M, Loupy Kelsey, Simpson Missy, Candia Julián, Mosley Thomas, Coresh Josef, Palta Priya, Ferrucci Luigi, Shapiro Allison, Williams Stephen A, Walker Keenan A
Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
SomaLogic Operating Co, Boulder, CO, USA.
Ann Neurol. 2024 Feb;95(2):260-273. doi: 10.1002/ana.26817. Epub 2023 Nov 2.
Few studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration.
In 706 cognitively normal adults, we examined whether 14 protein-based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma-based biomarkers of AD pathology (amyloid-β [Aβ] , tau phosphorylated at threonine-181 [pTau-181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aβ and tau. In a separate cohort (n = 11,285), we examined whether protein-based health indicators associated with neurodegeneration also predict 25-year dementia risk.
Greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with lower Aβ and higher pTau-181, NfL, and GFAP levels, even in individuals without cardiovascular or kidney disease. Proteomic indicators of body fat percentage, lean body mass, and visceral fat were associated with pTau-181, NfL, and GFAP, whereas resting energy rate was negatively associated with NfL and GFAP. Together, these health indicators predicted 12, 31, 50, and 33% of plasma Aβ , pTau-181, NfL, and GFAP levels, respectively. Only protein-based measures of cardiovascular risk were associated with reduced regional brain volumes; these measures predicted 25-year dementia risk, even among those without clinically defined cardiovascular disease.
Subclinical peripheral health may influence AD and neurodegenerative disease processes and relevant biomarker levels, particularly NfL. Cardiovascular health, even in the absence of clinically defined disease, plays a central role in brain aging and dementia. ANN NEUROL 2024;95:260-273.
很少有研究全面探讨健康和疾病风险如何影响阿尔茨海默病（AD）生物标志物。本研究考察了14种基于蛋白质的健康指标与AD及神经退行性变的血浆和神经影像学生物标志物之间的关联。
在706名认知正常的成年人中，我们考察了14种基于蛋白质的健康指数（即SomaSignal®检测）是否与同时测量的AD病理学血浆生物标志物（淀粉样β蛋白[Aβ]、苏氨酸181位点磷酸化的tau蛋白[pTau - 181]）、神经元损伤（神经丝轻链[NfL]）、反应性星形胶质细胞增生（胶质纤维酸性蛋白[GFAP]）、脑容量以及皮质Aβ和tau蛋白相关。在另一个队列（n = 11285）中，我们考察了与神经退行性变相关的基于蛋白质的健康指标是否也能预测25年痴呆风险。
即使在没有心血管疾病或肾脏疾病的个体中，基于蛋白质的心血管疾病、心力衰竭死亡率和肾脏疾病风险增加也与较低的Aβ水平以及较高的pTau - 181、NfL和GFAP水平相关。身体脂肪百分比、瘦体重和内脏脂肪的蛋白质组学指标与pTau - 181、NfL和GFAP相关，而静息能量率与NfL和GFAP呈负相关。这些健康指标共同分别预测了血浆Aβ、pTau - 181、NfL和GFAP水平的12%、31%、50%和33%。只有基于蛋白质的心血管风险指标与区域脑容量减少相关；这些指标预测了25年痴呆风险，即使在没有临床确诊心血管疾病的人群中也是如此。
亚临床外周健康状况可能影响AD和神经退行性疾病进程以及相关生物标志物水平，尤其是NfL。心血管健康，即使在没有临床确诊疾病的情况下，在脑衰老和痴呆中也起着核心作用。《神经病学年鉴》2024；95：260 - 273。
