摘要
背景：阿尔茨海默氏病（AD）是一种异质性神经退行性疾病。但是，很少有研究调查AD中的异源基因表达模式。 目的和方法：我们根据样本内相对表达顺序（REO）检查了AD四个大脑区域的基因表达模式。使用费舍尔精确检验，可以识别每个大脑区域的AD样本中REO明显高于非AD对照的基因对，并根据它们在AD样本之间的转录差异进行过滤。 AD的亚组通过聚类分析进行分类。 结果：基于REO的基因表达谱分析表明，AD患者中存在转录差异以及独特的疾病亚型。对于每个大脑区域，分为两个主要的亚组：一个亚组报告差异表达的基因与年龄相关基因重叠，另一个与神经炎症相关。 结论：AD转录亚组可能有助于了解AD的潜在发病机制，并为个性化的AD管理方法提供支持。
关键词: 阿尔茨海默病，相对表达顺序，衰老，基因表达，转录亚组，神经炎症。
[2]
Seltzer B, Sherwin I. A comparison of clinical features in early- and late-onset primary degenerative dementia. One entity or two? Arch Neurol 40(3): 143-6. (1983)
[3]
Schmidt C, Redyk K, Meissner B, Krack L, von Ahsen N, Roeber S, et al. Clinical features of rapidly progressive Alzheimer’s disease. Dement Geriatr Cogn Disord 29(4): 371-8. (2010)
[4]
Schmidt C, Wolff M, Weitz M, Bartlau T, Korth C, Zerr I. Rapidly progressive Alzheimer disease. Arch Neurol 68: 1124-30. (2011)
[5]
Persson K, Eldholm RS, Barca ML, Cavallin L, Ferreira D, Knapskog AB, et al. MRI-assessed atrophy subtypes in Alzheimer’s disease and the cognitive reserve hypothesis. PLoS One 12e0186595 (2017)
[6]
Park JY, Na HK, Kim S, Kim H, Kim HJ, Seo SW, et al. Robust identification of Alzheimer's disease subtypes based on cortical atrophy patterns. 7: 43270 (2017)
[7]
Squitti R, Simonelli I, Cassetta E, Lupoi D, Rongioletti M, Ventriglia M, et al. Patients with increased non-ceruloplasmin copper appear a distinct sub-group of Alzheimer’s disease: a neuroimaging study. Curr Alzheimer Res 14(12): 1318-26. (2017)
[8]
K. Iqbal, M. Flory, S. Khatoon, H. Soininen, T. Pirttila, M. Lehtovirta, et al. Subgroups of Alzheimer’s disease based on cerebrospinal fluid molecular markers. Ann Neurol 58: 748-57. (2005)
[9]
M. Li, H. Li, G. Hong, Z. Tang, G. Liu, X. Lin, et al. Identifying primary site of lung-limited Cancer of unknown primary based on relative gene expression orderings. BMC Cancer 19: 67. (2019)
[10]
Hong G, Li H, Li M, Zheng W, Li J, Chi M, et al. A simple way to detect disease-associated cellular molecular alterations from mixed-cell blood samples. Brief Bioinform 19: 613-21. (2018)
[11]
Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, et al. Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci USA 105: 15605-10. (2008)
[12]
Berchtold NC, Coleman PD, Cribbs DH, Rogers J, Gillen DL, Cotman CW. Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease. Neurobiol Aging 34: 1653-61. (2013)
[13]
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stats Soc: Series B (Methodological) 57: 289-300. (1995)
[14]
Shoffner JM. Oxidative phosphorylation defects and Alzheimer’s disease. Neurogenetics 1: 13-9. (1997)
[15]
Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer’s disease. J Neurochem 75: 436-9. (2000)
[16]
Bonet-Costa V, Pomatto LC, Davies KJ. The proteasome and oxidative stress in Alzheimer’s disease. Antioxid Redox Signal 25: 886-901. (2016)
[17]
Ovsepian SV, O’Leary VB, Zaborszky L, Ntziachristos V, Dolly JO. Synaptic vesicle cycle and amyloid beta: biting the hand that feeds. Alzheimers Dement 14: 502-13. (2018)
[18]
Hochstrasser T, Weiss E, Marksteiner J, Humpel C. Soluble cell adhesion molecules in monocytes of Alzheimer’s disease and mild cognitive impairment. Exp Gerontol 45(1): 70-4. (2010)
[19]
Marlow L, Cain M, Pappolla MA, Sambamurti K. Beta-secretase processing of the Alzheimer’s amyloid protein precursor (APP). J Mol Neurosci 20(3): 233-9. (2003)
[20]
Berridge MJ. Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia. Prion 7: 2-13. (2013)
[21]
Afanador L, Roltsch EA, Holcomb L, Campbell KS, Keeling DA, Zhang Y, et al. The Ca2+ sensor S100A1 modulates neuroinflammation, histopathology and Akt activity in the PSAPP Alzheimer’s disease mouse model. Cell Calcium 56: 68-80. (2014)
[22]
Afanador L, Keeling D, Campbell K, Campbell K, Roltsch E, Zimmer D. Aberrant calcium signaling modulates inflammatory and PI3/Akt pathways in Alzheimer’s disease. Alzheimers Dement 9: 352-52. (2013)
[24]
Biron KE, Dickstein DL, Gopaul R, Jefferies WA. Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer’s disease. PLoS One 6e23789 (2011)
[25]
Roberts TK, Eugenin EA, Lopez L, Romero IA, Wekslee BB, Couraud PO, et al. CCL2 disrupts the adherens junction: implications for neuroinflammation. Lab Invest 92: 1213-33. (2012)
[26]
Ostan R, Lanzarini C, Pini E, Scurti M, Vianello D, Bertarelli C, et al. Inflammaging and cancer: a challenge for the Mediterranean diet. Nutrients 7: 2589-621. (2015)
[27]
Piemontese L. An innovative approach for the treatment of Alzheimer’s disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions. Neural Regen Res 14: 43-5. (2019)
Related Books
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research-Dementia
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Article Metrics
35
5