Blood CDKN2A Gene Expression in Aging and Neurodegenerative Diseases

Abstract

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. Objective: 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). Methods: 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. Results: 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. Conclusion: 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.

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

“…It is worth noting that CDKN2A is a Protein Coding gene. Diseases related to CDKN2A include Cutaneous Malignant Melanoma 15–18 . Among its associated pathways are DNA Damage Response and Mitotic G1‐G1/S phases 19 .…”

“…Hence, cellular senescence might exert a basic effect on the occurrence and development of HNSCC. We [15][16][17][18] Among its associated pathways are DNA Damage Response and Mitotic G1-G1/S phases. 19 IL1A (Interleukin 1 Alpha) is related to cytokine activity and interleukin-1 receptor binding and its associated pathways are IL1α-NF-κB pathway and cytokine signaling in Immune system.…”

Towards an understanding of the pathological basis of senile depression and incident dementia: Implications for treatment

“…Similarities between these disorders include neuroinflammation, elevated proinflammatory cytokines, decreased neurotrophic factors, abnormal synaptic function, deep white matter lesions, and increased brain atrophy. If depression is a prodrome of dementia, and if it is present 10 years before the onset of dementia, then several biomarkers may be useful for diagnosing SD 34–37 …”

“…If depression is a prodrome of dementia, and if it is present 10 years before the onset of dementia, then several biomarkers may be useful for diagnosing SD. [34][35][36][37] Imbalance of monoaminergic systems The monoamine hypothesis is the most explored putative explanation for the pathophysiology of MDD. Consequently, monoamine neurotransmitters, including serotonin, norepinephrine, and dopamine, play a pivotal role in the current pharmacological treatment of depression.…”

“…If depression is a prodrome of dementia, and if it is present 10 years before the onset of dementia, then several biomarkers may be useful for diagnosing SD. 34 , 35 , 36 , 37 …”