Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly indviduals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 (1.7) years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in the cognition (Pre-Alzheimer's Clinical Composite; R2=0.14, 95% CI [0.12-0.17]; P<0.0001) and subsequent AD dementia (AUC=0.82, 95% CI [0.77-0.91], P<0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P<0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P<0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.

中文翻译：

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阿尔茨海默氏病的血浆生物标志物可预测认知能力下降，并可以改善无认知障碍老年人的临床试验

淀粉样蛋白，tau蛋白和神经变性（ATN）的血浆生物标志物需要在认知能力受损（CU）的老年人中进行表征。因此，我们测试了淀粉样蛋白-β（Aβ）42/40，磷酸化-tau217（P-tau217）和神经丝轻度（NfL）的血浆测量是否能共同预测435 CU患者的临床恶化，平均随访4.8（1.7）年在BioFINDER研究中。三种血浆生物标志物和基本人口统计学指标的结合可以最好地预测认知的变化（阿尔茨海默氏综合症前； R2 = 0.14，95％CI [0.12-0.17]； P <0.0001）和随后的AD痴呆（AUC = 0.82、95） ％CI [0.77-0.91]，P <0.0001）。在模拟的临床试验中，结合所有三种血浆生物标志物的筛选算法将所需的样本量减少了70％（95％CI [54-81]； P <0.001），并且将其视为试验终点，有63％（95％CI [53-70]，P <0.001），随后的AD痴呆为试验终点。血浆ATN生物标记物在认知能力未受损的人群中显示出有用性，并且可以使大型临床试验更加可行且更具成本效益。