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. 2019 Feb 18;20(4):878.
doi: 10.3390/ijms20040878.

Hippocampal LMNA Gene Expression is Increased in Late-Stage Alzheimer's Disease

Iván Méndez-López  1   2 , Idoia Blanco-Luquin  3 , Javier Sánchez-Ruiz de Gordoa  4   5 , Amaya Urdánoz-Casado  6 , Miren Roldán  7 , Blanca Acha  8 , Carmen Echavarri  9   10 , Victoria Zelaya  11 , Ivonne Jericó  12 , Maite Mendioroz  13   14
Affiliations

Hippocampal LMNA Gene Expression is Increased in Late-Stage Alzheimer's Disease

Iván Méndez-López et al. Int J Mol Sci. .

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.

Keywords: Alzheimer’s disease; LMNA; aging; hippocampus; lamin A; lamin C; lamins; tauopathy.

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Conflict of interest statement

The authors declare no conflict of interest

Figures

Figure 1
Figure 1
mRNA levels of lamin genes across Alzheimer’s disease (AD) stages. AD hippocampal samples were sorted in three levels [low (n = 14), intermediate (n = 6), and high (n = 8)] of AD neuropathological severity based on ABC score. According to that, mRNA expression levels are shown for each group and gene by bar graphs. The upper row shows the map for each gene. Where black squares represent exons, the thin arrow represents transcription start site for each gene; black rectangular arrow-boxes below the gene map denote amplicons of the RT-qPCR. (A) The LMNA gene graph shows a significant increase in expression among ABC stages. (B) A statistical tendency (p-value = 0.052) across ABC stages was found for the LMNB1 gene, the high ABC stage being the one with highest expression. (C) The LMNB2 gene did not show any difference between ABC stages. Boxes represent percentage of lamin genes expression relative to the geometric mean of GAPDH and ACTB housekeeping genes expression levels. Bars represent the standard error of the mean. * p-value < 0.05.
Figure 2
Figure 2
Western blot analysis of Lamin A/C proteins in human hippocampus. (A) Both lamin A and lamin C are expressed in control hippocampal samples. (B) Increasing tendency of lamin A and C protein expression from low to high ABC stages. GAPDH was used as a control. GAPDH: 37 kDa, Lamin A/C: 70-65 kDa.
Figure 3
Figure 3
Scatter-plots showing the correlation level between LMNA mRNA levels and age. (A) No association was found between age and LMNA mRNA expression within the whole sample set (controls and Alzheimer’s patients). (B) Control group presented a medium significant positive correlation between LMNA mRNA levels and age. (C) No correlation within the AD group was observed between LMNA mRNA and age. Dots represent each sample according to percentage of LMNA expression relative to the geometric mean of GAPDH and ACTB housekeeping genes expression and their age. The straight line shows the regression line of LMNA mRNA levels and age. AD = Alzheimer’s disease.
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