INTRODUCTIONAlzheimer'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.METHODSBlood 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.RESULTSHeritability 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.DISCUSSIONThe 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.

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阿尔茨海默病血浆生物标志物的遗传性：核双胞胎家族设计


引言阿尔茨海默病 （AD） 是一种高度遗传的疾病 （60%-80%）。β 淀粉样蛋白 （Aβ） 42/40、神经丝轻链 （NfL） 和神经胶质纤维酸性蛋白 （GFAP） 是 AD 的血浆生物标志物。了解这些标志物的差异来源将有助于临床生物标志物研究。方法在 Simoa HD-X 上分析双胞胎及其家庭 （同卵双胞胎：1574，异卵双胞胎：1266，其他：3657） 的 Aβ42/40、NfL 和 GFAP 浓度。双胞胎家庭模型用于估计对生物标志物水平方差的成比例遗传贡献。结果Aβ42/40 的免疫力估计值为 16%，NfL 为 42%，GFAP 为 60%。NfL 和 GFAP 彼此显著相关 （0.37），但与 Aβ42/40 无关。NfL/GFAP 和 Aβ42/40 之间缺乏相关性表明这些标志物可能位于不同的生物途径上。亮点 发现神经胶质纤维酸性蛋白 （60%） 、神经丝轻链 （42%） 和淀粉样蛋白 β （Aβ） 42/40 （16%） 血浆水平具有遗传性。Aβ42/40 血浆水平对个体特异性环境影响敏感。