Abstract
Lamins are fibrillary proteins that are crucial in maintaining nuclear shape and function. Recently, B-type lamin dysfunction has been linked to tauopathies. However, the role of A-type lamin in neurodegeneration is still obscure. Here, we examined A-type and B-type lamin expression levels by RT-qPCR in Alzheimer’s disease (AD) patients and controls in the hippocampus, the core of tau pathology in the brain. LMNA, LMNB1, and LMNB2 genes showed moderate mRNA levels in the human hippocampus with highest expression for the LMNA gene. Moreover, LMNA mRNA levels were increased at the late stage of AD (1.8-fold increase; p-value < 0.05). In addition, a moderate positive correlation was found between age and LMNA mRNA levels (Pearson’s r = 0.581, p-value = 0.018) within the control hippocampal samples that was not present in the hippocampal samples affected by AD. A-type and B-type lamin genes are expressed in the human hippocampus at the transcript level. LMNA mRNA levels are up-regulated in the hippocampal tissue in late stages of AD. The effect of age on increasing LMNA expression levels in control samples seems to be disrupted by the development of AD pathology.
Highlights
The nuclear lamina is a reticular structure attached to the internal nuclear membrane
We measured mRNA expression levels of LMNA, LMNB1, and LMNB2 genes by real time quantitative PCR (RT-qPCR) in human hippocampal samples from Alzheimer’s disease (AD) patients compared to controls
An important finding of this study is that all lamin genes including LMNA show moderate mRNA expression levels in the human hippocampus
Summary
The nuclear lamina is a reticular structure attached to the internal nuclear membrane. It is essential for the maintenance of nuclear architecture and morphology and participates in critical cellular functions, such as DNA replication, transcription, chromatin organization, nuclear differentiation, or signal transduction, among others. The LMNA gene encodes A-type lamin: lamin A/C, whereas LMNB1 and LMNB2 genes encode B-type lamins: lamin B1 and lamina B2 respectively. More than 20 human diseases have been related to mutations in these genes. LMNB1 gene duplication causes autosomal dominant leukodystrophy with autonomic disease (ADLD) [2] whereas homozygous missense mutations in the LMNB2 gene have been associated with an acquired partial lipodystrophy called Barraquer–Simons syndrome and with progressive myoclonus epilepsy with early ataxia [3,4]
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