Tomassen Jori, den Braber Anouk, van der Landen Sophie M, Konijnenberg Elles, Teunissen Charlotte E, Vermunt Lisa, de Geus Eco J C, Boomsma Dorret I, Scheltens Philip, Tijms Betty M, Visser Pieter Jelle
Alzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The Netherlands.
Amsterdam Neuroscience Neurodegeneration Amsterdam The Netherlands.
Alzheimers Dement (N Y). 2022 Sep 20;8(1):e12346. doi: 10.1002/trc2.12346. eCollection 2022.
The contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins.
We included 122 cognitively normal monozygotic twins (51 pairs) with a follow-up of 4.3 ± 0.4 years. We first tested associations of baseline CSF Aβ1-42/1-40 ratio, total tau (t-tau), and 181-phosphorylated-tau (p-tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses.
Baseline abnormal amyloid-β and tau CSF markers predicted steeper decline on memory ( ≤ .003) and language ( ≤ 0.04). Amyloid-β and p-tau markers in one twin predicted decline in memory in the co-twin and tau markers in one twin predicted decline in language in the co-twin ( range -0.26,0.39; 's ≤ .02).
These results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid-β and tau regulation.
在临床前阿尔茨海默病中，遗传和环境因素对脑脊液（CSF）生物标志物与认知衰退之间关系的影响尚不清楚。我们在最初认知正常的同卵双胞胎中对此进行了研究。
我们纳入了122名认知正常的同卵双胞胎（51对），随访时间为4.3±0.4年。我们首先使用线性混合模型测试基线脑脊液Aβ1-42/1-40比值、总tau蛋白（t-tau）和181-磷酸化tau蛋白（p-tau）状态与随后认知衰退的关联，然后进行双胞胎特异性分析。
基线异常淀粉样β蛋白和tau蛋白脑脊液标志物预示着记忆（≤0.003）和语言（≤0.04）方面的衰退更为明显。一个双胞胎中的淀粉样β蛋白和p-tau蛋白标志物预示着另一个双胞胎的记忆衰退，而一个双胞胎中的tau蛋白标志物预示着另一个双胞胎的语言衰退（范围为-0.26,0.39；P值≤0.02）。
这些结果表明，记忆和语言衰退是阿尔茨海默病的早期特征，部分由影响淀粉样β蛋白和tau蛋白调节的相同遗传因素决定。
