血浆β淀粉样蛋白40/42、磷酸化tau蛋白181和神经丝轻链与世贸中心救援人员的认知障碍和神经病理变化相关：一项关于中年暴露与认知衰老的前瞻性队列研究。
Plasma amyloid beta 40/42, phosphorylated tau 181, and neurofilament light are associated with cognitive impairment and neuropathological changes among World Trade Center responders: A prospective cohort study of exposures and cognitive aging at midlife.
作者信息
Kritikos Minos, Diminich Erica D, Meliker Jaymie, Mielke Michelle, Bennett David A, Finch Caleb E, Gandy Sam E, Carr Melissa A, Yang Xiaohua, Kotov Roman, Kuan Pei-Fen, Bromet Evelyn J, Clouston Sean A P, Luft Benjamin J
机构信息
Program in Public Health and Department of Family Population, and Preventive Medicine Renaissance School of Medicine at Stony Brook University Stony Brook New York USA.
Department of Epidemiology and Prevention Wake Forest University School of Medicine Winston-Salem North Carolina USA.
出版信息
Alzheimers Dement (Amst). 2023 Mar 8;15(1):e12409. doi: 10.1002/dad2.12409. eCollection 2023 Jan-Mar.
INTRODUCTION
World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology.
METHODS
Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aβ)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia.
RESULTS
Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aβ40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data ( = 75), Aβ40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82]).
DISCUSSION
WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease.
引言
世界贸易中心（WTC）救援人员面临轻度认知障碍（MCI）和痴呆症的高风险，尽管其病因仍未得到充分描述。本研究调查了WTC暴露和慢性创伤后应激障碍（PTSD）是否与阿尔茨海默病（AD）神经病理学特征性的血浆生物标志物相关。
方法
符合条件的参与者包括接受过WTC暴露且有基线认知评估和可用血浆样本的个体。我们检测了淀粉样β蛋白（Aβ）40/42比值、磷酸化tau蛋白181（p-tau181）和神经丝轻链（NfL）的水平，以及它们与WTC暴露（现场停留时间≥15周、尘云）、《精神疾病诊断与统计手册》第4版PTSD的PTSD症状清单，以及淀粉样蛋白/ tau蛋白/神经退行性变（AT[N]）谱分类之间的关联。多项逻辑回归评估了生物标志物是否能预测MCI或痴呆风险增加。
结果
在1179名符合条件的救援人员中，93.0%为男性，平均（标准差）年龄56.6岁（7.8）。Aβ40/42、p-tau181和NfL相互关联且随年龄增加。在有可用神经影像学数据的救援人员亚组分析中（n = 75），Aβ40/42和p-tau181还与海马体积减小相关（斯皮尔曼相关系数r = -0.3）。总体而言，58.08%的痴呆症救援人员有≥1种生物标志物升高，3.45%的人员所有生物标志物均升高。共有248人（21.05%）患有MCI，70人（5.94%）患有痴呆症。痴呆风险增加与血浆AT（N）谱T+或A+N+相关。现场暴露≥15周与T+独立相关（调整风险比[aRR] = 1.03 [1.01 - 1.05]，P = 0.009），以及T+N+谱（aRR = 2.34 [1.12 - 4.87]）。PTSD的存在与A+风险独立相关（aRR = 1.77 [1.11 - 2.82]）。
讨论
WTC暴露和慢性PTSD与与神经退行性疾病一致的血浆生物标志物相关。
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