Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
J Alzheimers Dis. 2021;82(4):1737-1744. doi: 10.3233/JAD-210483.
Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging.
This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer's disease (AD).
The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson's disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined.
A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman's rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates.
Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.
细胞周期蛋白依赖性激酶抑制剂 2A(CDKN2A)是细胞衰老和老化过程中的一个重要基因。
本研究评估了血液 CDKN2A mRNA 表达水平和甲基化状态作为衰老和阿尔茨海默病(AD)发病机制的潜在生物标志物的效用。
在 45 名健康受试者中检查了 CDKN2A mRNA 表达水平与年龄之间的相关性,然后比较了 46 名 AD 患者、20 名 AD 轻度认知障碍患者、21 名帕金森病患者、21 名路易体痴呆患者和 55 名年龄较大的健康对照组之间的 mRNA 表达水平。还检查了已知影响其表达水平的 CDKN2A 基因第二外显子的甲基化率。
发现 CDKN2A mRNA 表达水平与年龄之间存在显著相关性(Spearman 秩相关系数:r = 0.407,p = 0.005)。AD 患者血液中的 CDKN2A mRNA 表达水平显著降低,尽管健康对照组的表达水平随着年龄的增长而显著增加。此外,只有在 AD 患者中,CDKN2A mRNA 表达水平与甲基化率呈显著正相关。
虽然需要进一步的研究来阐明血液中 CDKN2A 基因表达与其他神经退行性疾病发展之间的关系,但血液中的 CDKN2A mRNA 表达可能是区分 AD 与正常衰老和其他神经退行性疾病的生物标志物。