The Neurology Centre, Dongzhimen Hospital, Beijing University of Chinese Medicine, 100700, Beijing, China.
Department of Neurology, Beijing Hospital, Beijing, China.
BMC Geriatr. 2022 Jun 1;22(1):471. doi: 10.1186/s12877-022-03163-8.
Repressor element 1-silencing transcription (REST)/neuron-restrictive silencer factor is considered a new therapeutic target for neurodegenerative disorders such as Alzheimer's disease (AD). However, the relationship between AD and REST remains unclear. This study aimed to 1) examine plasma REST levels and REST gene levels in AD patients and 2) further explore the pathological relationships between REST protein levels and cognitive decline in clinical conditions, including medial temporal lobe atrophy.
Participants (n = 252, mean age 68.95 ± 8.78 years) were recruited in Beijing, China, and then divided into a normal cognition (NC) group (n = 89), an amnestic mild cognitive impairment (aMCI) group (n = 79), and an AD dementia group (n = 84) according to diagnostic criteria. All participants underwent neuropsychological assessments, laboratory tests, and neuroimaging scans (magnetic resonance imaging) at baseline. Plasma REST protein levels and the distribution of REST single nucleotide polymorphisms (SNPs) were compared among the three groups. Correlations between cognitive function, neuro-imaging results, and REST levels were determined by a multivariate linear regression analysis.
The plasma REST levels in both the NC group (430.30 ± 303.43)pg/ml and aMCI group (414.27 ± 263.39)pg/ml were significantly higher than that in the AD dementia group (NC vs AD dementia group, p = 0.034; aMCI vs AD dementia group, p = 0.033). There was no significant difference between the NC and aMCI groups (p = 0.948). No significant difference was found among the three groups regarding the genotype distribution (rs2227902 and rs3976529 SNPs) of the REST gene. The REST level was correlated with the left medial temporal lobe atrophy index (r = 0.306, p = 0.023). After 6 months of follow-up, the REST level in the NC group was positively correlated with the change in the Mini-Mental State Examination score (r = 0.289, p = 0.02).
The plasma REST protein level is decreased in AD dementia patients, which is associated with memory impairment and left temporal lobe atrophy and may have potential value for clinical diagnosis of AD dementia.
抑制元件 1-沉默转录因子（REST）/神经元抑制因子被认为是阿尔茨海默病（AD）等神经退行性疾病的新治疗靶点。然而，AD 与 REST 之间的关系尚不清楚。本研究旨在：1）检测 AD 患者血浆 REST 水平和 REST 基因水平；2）进一步探讨 REST 蛋白水平与临床条件下认知能力下降之间的病理关系，包括内侧颞叶萎缩。
参与者（n=252，平均年龄 68.95±8.78 岁）在北京招募，然后根据诊断标准分为正常认知（NC）组（n=89）、遗忘型轻度认知障碍（aMCI）组（n=79）和 AD 痴呆组（n=84）。所有参与者均在基线时接受神经心理学评估、实验室检查和神经影像学扫描（磁共振成像）。比较三组之间的血浆 REST 蛋白水平和 REST 单核苷酸多态性（SNP）分布。通过多元线性回归分析确定认知功能、神经影像学结果与 REST 水平之间的相关性。
NC 组（430.30±303.43）pg/ml 和 aMCI 组（414.27±263.39）pg/ml 的血浆 REST 水平均显著高于 AD 痴呆组（NC 与 AD 痴呆组比较，p=0.034；aMCI 与 AD 痴呆组比较，p=0.033）。NC 组和 aMCI 组之间无显著差异（p=0.948）。三组间 REST 基因的基因型分布（rs2227902 和 rs3976529 SNPs）无显著差异。REST 水平与左侧内侧颞叶萎缩指数呈正相关（r=0.306，p=0.023）。经过 6 个月的随访，NC 组的 REST 水平与简易精神状态检查评分的变化呈正相关（r=0.289，p=0.02）。
AD 痴呆患者的血浆 REST 蛋白水平降低，与记忆障碍和左侧颞叶萎缩有关，对 AD 痴呆的临床诊断可能具有潜在价值。
