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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Feb 21

PMID 30781626

Citations 12

Authors

Ivan Mendez-Lopez

Idoia Blanco-Luquin

Javier Sanchez-Ruiz de Gordoa

Amaya Urdanoz-Casado

Miren Roldan

Blanca Acha

Carmen Echavarri

Victoria Zelaya

Ivonne Jerico

Maite Mendioroz

Affiliations

Soon will be listed here.

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. , and genes showed moderate mRNA levels in the human hippocampus with highest expression for the gene. Moreover, mRNA levels were increased at the late stage of AD (1.8-fold increase; -value < 0.05). In addition, a moderate positive correlation was found between age and mRNA levels (Pearson's = 0.581, -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. mRNA levels are up-regulated in the hippocampal tissue in late stages of AD. The effect of age on increasing expression levels in control samples seems to be disrupted by the development of AD pathology.

Citing Articles

Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.

Fisher R, Torrente M Front Mol Neurosci. 2024; 17:1456052.

PMID: 39346681 PMC: 11427407. DOI: 10.3389/fnmol.2024.1456052.

Network-based identification and mechanism exploration of active ingredients against Alzheimer's disease via targeting endoplasmic reticulum stress from traditional chinese medicine.

Dai Z, Hu T, Wei J, Wang X, Cai C, Gu Y Comput Struct Biotechnol J. 2024; 23:506-519.

PMID: 38261917 PMC: 10796977. DOI: 10.1016/j.csbj.2023.12.017.

Discovery of a Small-Molecule Modulator of the Autophagy-Lysosome Pathway That Targets Lamin A/C and LAMP1, Induces Autophagic Flux, and Affects Lysosome Positioning in Neurons.

Hippman R, Snead A, Petros Z, Korkmaz-Vaisys M, Patel S, Sotelo D ACS Chem Neurosci. 2023; 14(24):4363-4382.

PMID: 38069806 PMC: 10739612. DOI: 10.1021/acschemneuro.3c00573.

Development of an accelerated cellular model for early changes in Alzheimer's disease.

Xue H, Gate 3rd S, Gentry E, Losert W, Cao K Sci Rep. 2023; 13(1):18384.

PMID: 37884611 PMC: 10603068. DOI: 10.1038/s41598-023-45826-5.

Can accelerated ageing models inform us on age-related tauopathies?.

Han Z, Fleet A, Larrieu D Aging Cell. 2023; 22(5):e13830.

PMID: 37013265 PMC: 10186612. DOI: 10.1111/acel.13830.

References

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Thal D, Rub U, Orantes M, Braak H . Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002; 58(12):1791-800. DOI: 10.1212/wnl.58.12.1791. View

De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I . Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003; 300(5628):2055. DOI: 10.1126/science.1084125. View

Eriksson M, Brown W, Gordon L, Glynn M, Singer J, Scott L . Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003; 423(6937):293-8. PMC: 10540076. DOI: 10.1038/nature01629. View

Scaffidi P, Misteli T . Lamin A-dependent nuclear defects in human aging. Science. 2006; 312(5776):1059-63. PMC: 1855250. DOI: 10.1126/science.1127168. View

Hegele R, Cao H, Liu D, Costain G, Charlton-Menys V, Rodger N . Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet. 2006; 79(2):383-9. PMC: 1559499. DOI: 10.1086/505885. View

Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K . Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006; 112(4):389-404. PMC: 3906709. DOI: 10.1007/s00401-006-0127-z. View

Padiath Q, Saigoh K, Schiffmann R, Asahara H, Yamada T, Koeppen A . Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet. 2006; 38(10):1114-23. DOI: 10.1038/ng1872. View

Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A . Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants. Hum Mol Genet. 2007; 16(8):865-73. DOI: 10.1093/hmg/ddm031. View

10.

Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-59. DOI: 10.1007/BF00308809. View

11.

Bell J, Alafuzoff I, Al-Sarraj S, Arzberger T, Bogdanovic N, Budka H . Management of a twenty-first century brain bank: experience in the BrainNet Europe consortium. Acta Neuropathol. 2008; 115(5):497-507. DOI: 10.1007/s00401-008-0360-8. View

12.

Schjeide B, McQueen M, Mullin K, DiVito J, Hogan M, Parkinson M . Assessment of Alzheimer's disease case-control associations using family-based methods. Neurogenetics. 2008; 10(1):19-25. PMC: 2841132. DOI: 10.1007/s10048-008-0151-3. View

13.

Lace G, Savva G, Forster G, De Silva R, Brayne C, Matthews F . Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study. Brain. 2009; 132(Pt 5):1324-34. DOI: 10.1093/brain/awp059. View

14.

Mirra S, HEYMAN A, McKeel D, SUMI S, Crain B, Brownlee L . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991; 41(4):479-86. DOI: 10.1212/wnl.41.4.479. View

15.

Ragnauth C, Warren D, Liu Y, McNair R, Tajsic T, Figg N . Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation. 2010; 121(20):2200-10. DOI: 10.1161/CIRCULATIONAHA.109.902056. View

16.

Wegner L, Anthonsen S, Bork-Jensen J, Dalgaard L, Hansen T, Pedersen O . LMNA rs4641 and the muscle lamin A and C isoforms in twins--metabolic implications and transcriptional regulation. J Clin Endocrinol Metab. 2010; 95(8):3884-92. DOI: 10.1210/jc.2009-2675. View

17.

Belbin O, Carrasquillo M, Crump M, Culley O, Hunter T, Ma L . Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease. Hum Genet. 2010; 129(3):273-82. PMC: 3036835. DOI: 10.1007/s00439-010-0924-2. View

18.

Yeh H, Hou S, Yen F, Hong C, Liou Y, Yang A . Polymorphisms in LMNA and near a SERPINA13 gene are not associated with cognitive performance in Chinese elderly males without dementia. Neurosci Lett. 2011; 504(1):32-4. DOI: 10.1016/j.neulet.2011.08.051. View

19.

Montine T, Phelps C, Beach T, Bigio E, Cairns N, Dickson D . National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2011; 123(1):1-11. PMC: 3268003. DOI: 10.1007/s00401-011-0910-3. View

20.

Hattori A, Komaki H, Kawatani M, Sakuma H, Saito Y, Nakagawa E . A novel mutation in the LMNA gene causes congenital muscular dystrophy with dropped head and brain involvement. Neuromuscul Disord. 2012; 22(2):149-51. DOI: 10.1016/j.nmd.2011.08.009. View