阿尔茨海默病血浆生物标志物的遗传度：一项核孪生家族研究设计。
Heritability of Alzheimer's disease plasma biomarkers: A nuclear twin family design.
作者信息
Rousset Rebecca Z, den Braber Anouk, Verberk Inge M W, Boonkamp Lynn, Wilson David H, Ligthart Lannie, Teunissen Charlotte E, de Geus Eco J C
机构信息
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Alzheimer Center, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
出版信息
Alzheimers Dement. 2025 Jan;21(1):e14269. doi: 10.1002/alz.14269. Epub 2024 Nov 26.
INTRODUCTION
Alzheimer's disease (AD) is a highly heritable disease (60%-80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.
METHODS
Blood concentrations of Aβ42/40, NfL, and GFAP of twins and their families (monozygotic twins: 1574, dizygotic twins: 1266, other: 3657) were analyzed on the Simoa HD-X. Twin-family models were used to estimate proportional genetic contributions to the variance in biomarker levels.
RESULTS
Heritability estimates were 16% for Aβ42/40, 42% for NfL, and 60% for GFAP. NfL and GFAP were significantly correlated with each other (0.37) but not with Aβ42/40.
DISCUSSION
The heritability of Aβ42/40 (16%) is lower than the heritability of AD, suggesting strong environmental influences on this biomarker. The lack of correlation between NfL/GFAP and Aβ42/40 indicates these markers may be on different biological pathways.
HIGHLIGHTS
Heritability is found for glial fibrillary acidic protein (60%), neurofilament light chain (42%), and amyloid beta (Aβ) 42/40 (16%) plasma levels. Aβ42/40 plasma levels are sensitive to person-specific environmental influences.
引言
阿尔茨海默病（AD）是一种高度可遗传的疾病（遗传率为60%-80%）。淀粉样β蛋白（Aβ）42/40、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）是AD的血浆生物标志物。了解这些标志物的变异来源将有助于临床生物标志物研究。
方法
在Simoa HD-X上分析了双胞胎及其家庭成员（同卵双胞胎：1574例，异卵双胞胎：1266例，其他：3657例）的血液中Aβ42/40、NfL和GFAP的浓度。采用双生子-家系模型来估计生物标志物水平变异的遗传贡献率。
结果
Aβ42/40的遗传率估计为16%，NfL为42%，GFAP为60%。NfL和GFAP彼此显著相关（0.37），但与Aβ42/40不相关。
讨论
Aβ42/40的遗传率（16%）低于AD的遗传率，表明该生物标志物受环境影响较大。NfL/GFAP与Aβ42/40之间缺乏相关性，表明这些标志物可能处于不同的生物学途径。
要点
发现胶质纤维酸性蛋白（60%）、神经丝轻链（42%）和淀粉样β蛋白（Aβ）42/40（16%）的血浆水平具有遗传率。Aβ42/40血浆水平对个体特异性环境影响敏感。
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