Item request has been placed!
×
Item request cannot be made.
×
Processing Request
CD163-Mediated Small-Vessel Injury in Alzheimer's Disease: An Exploration from Neuroimaging to Transcriptomics.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Additional Information
- Corporate Authors:
- Source:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
- Publication Information:
Original Publication: Basel, Switzerland : MDPI, [2000-
- Subject Terms:
- Abstract:
Patients with Alzheimer's disease (AD) often present with imaging features indicative of small-vessel injury, among which, white-matter hyperintensities (WMHs) are the most prevalent. However, the underlying mechanism of the association between AD and small-vessel injury is still obscure. The aim of this study is to investigate the mechanism of small-vessel injury in AD. Differential gene expression analyses were conducted to identify the genes related to WMHs separately in mild cognitive impairment (MCI) and cognitively normal (CN) subjects from the ADNI database. The WMH-related genes identified in patients with MCI were considered to be associated with small-vessel injury in early AD. Functional enrichment analyses and a protein-protein interaction (PPI) network were performed to explore the pathway and hub genes related to the mechanism of small-vessel injury in MCI. Subsequently, the Boruta algorithm and support vector machine recursive feature elimination (SVM-RFE) algorithm were performed to identify feature-selection genes. Finally, the mechanism of small-vessel injury was analyzed in MCI from the immunological perspectives; the relationship of feature-selection genes with various immune cells and neuroimaging indices were also explored. Furthermore, 5×FAD mice were used to demonstrate the genes related to small-vessel injury. The results of the logistic regression analyses suggested that WMHs significantly contributed to MCI, the early stage of AD. A total of 276 genes were determined as WMH-related genes in patients with MCI, while 203 WMH-related genes were obtained in CN patients. Among them, only 15 genes overlapped and were thus identified as the crosstalk genes. By employing the Boruta and SVM-RFE algorithms, CD163, ALDH3B1, MIR22HG, DTX2, FOLR2, ALDH2, and ZNF23 were recognized as the feature-selection genes linked to small-vessel injury in MCI. After considering the results from the PPI network, CD163 was finally determined as the critical WMH-related gene in MCI. The expression of CD163 was correlated with fractional anisotropy (FA) values in regions that are vulnerable to small-vessel injury in AD. The immunostaining and RT-qPCR results from the verifying experiments demonstrated that the indicators of small-vessel injury presented in the cortical tissue of 5×FAD mice and related to the upregulation of CD163 expression. CD163 may be the most pivotal candidates related to small-vessel injury in early AD.
- References:
Neurotoxicology. 2018 Sep;68:19-24. (PMID: 29936317)
Metab Brain Dis. 2022 Jan;37(1):39-50. (PMID: 34406560)
Cancer Lett. 2008 Aug 8;266(2):135-43. (PMID: 18384939)
Transl Res. 2023 Apr;254:41-53. (PMID: 36529160)
Neuroimage. 2012 Aug 15;62(2):782-90. (PMID: 21979382)
Physiol Genomics. 2014 Nov 15;46(22):821-32. (PMID: 25271210)
Comput Biol Med. 2023 Mar;154:106621. (PMID: 36746116)
Neurobiol Aging. 2023 Nov;131:144-152. (PMID: 37639768)
Nature. 2001 Jan 11;409(6817):198-201. (PMID: 11196644)
Alzheimers Dement. 2022 Mar;18(3):422-433. (PMID: 34322985)
Eur J Neurol. 2021 Jun;28(6):1931-1938. (PMID: 33377242)
Lancet Neurol. 2013 Aug;12(8):822-38. (PMID: 23867200)
Neurotherapeutics. 2007 Jul;4(3):316-29. (PMID: 17599699)
J Alzheimers Dis. 2023;91(2):795-804. (PMID: 36502328)
Neurology. 2021 Jan 12;96(2):e193-e202. (PMID: 33046608)
BMC Syst Biol. 2014;8 Suppl 4:S11. (PMID: 25521941)
Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778)
Eur J Pharmacol. 2020 Jun 15;877:173090. (PMID: 32234529)
Am J Pathol. 2021 Nov;191(11):1888-1905. (PMID: 34331941)
Alzheimers Dement. 2015 Jul;11(7):865-84. (PMID: 26194320)
Cell. 2022 Mar 31;185(7):1189-1207.e25. (PMID: 35325594)
Free Radic Biol Med. 2010 Nov 15;49(9):1432-43. (PMID: 20699116)
Lancet Public Health. 2020 Dec;5(12):e661-e671. (PMID: 33271079)
Neurobiol Aging. 2023 May;125:62-73. (PMID: 36842362)
Acta Neuropathol. 2021 Dec;142(6):937-950. (PMID: 34608542)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Lancet. 2021 Apr 24;397(10284):1577-1590. (PMID: 33667416)
Brain. 2019 Aug 1;142(8):2483-2491. (PMID: 31199475)
Nat Rev Neurosci. 2011 Nov 03;12(12):723-38. (PMID: 22048062)
Front Hum Neurosci. 2015 Jun 30;9:386. (PMID: 26175682)
Mov Disord. 2019 Nov;34(11):1711-1721. (PMID: 31449711)
Acta Neuropathol. 2020 Oct;140(4):477-493. (PMID: 32840654)
J Immunol. 2012 Aug 15;189(4):1946-54. (PMID: 22778395)
Neuroimage Clin. 2013 Jul 27;3:180-95. (PMID: 24179862)
Brief Bioinform. 2021 Sep 2;22(5):. (PMID: 33866355)
Neuroimage Clin. 2019;24:101945. (PMID: 31374399)
J Proteomics. 2021 Feb 10;232:104023. (PMID: 33130111)
Brief Bioinform. 2022 Mar 10;23(2):. (PMID: 35183059)
Nature. 2022 Mar;603(7903):885-892. (PMID: 35165441)
Int J Dev Neurosci. 2001 Feb;19(1):21-35. (PMID: 11226752)
J Alzheimers Dis. 2022;87(2):863-871. (PMID: 35404279)
Curr Opin Clin Nutr Metab Care. 2004 Nov;7(6):659-64. (PMID: 15534434)
Aging (Albany NY). 2020 May 10;12(9):8506-8522. (PMID: 32388497)
Neurology. 2006 Dec 26;67(12):2192-8. (PMID: 17190943)
BMJ Open Sci. 2020 Jul 20;4(1):e100115. (PMID: 34095516)
Acta Neuropathol Commun. 2014 Feb 14;2:21. (PMID: 24528486)
J Exp Clin Cancer Res. 2020 Dec 3;39(1):271. (PMID: 33267888)
Annu Rev Pathol. 2015;10:291-319. (PMID: 25387055)
Cancer Res. 2009 Dec 15;69(24):9395-403. (PMID: 19951991)
Korean J Anesthesiol. 2018 Oct;71(5):353-360. (PMID: 30157585)
Brain Res. 2005 Nov 9;1061(2):114-7. (PMID: 16256963)
Alzheimers Dement. 2023 Apr;19(4):1503-1517. (PMID: 36047604)
J Biol Chem. 2003 Jun 13;278(24):21930-7. (PMID: 12670957)
Neurosci Lett. 2008 May 16;436(3):317-20. (PMID: 18406523)
J Neurol. 2023 Oct;270(10):4985-4994. (PMID: 37368130)
Arthritis Rheumatol. 2022 May;74(5):892-901. (PMID: 34907668)
J Clin Invest. 2018 Mar 1;128(3):1106-1124. (PMID: 29457790)
- Grant Information:
Natural Science Funding; No. 23ZR1439200 Shanghai Science and Technology Committee Project; 2022YFA1603604 [ZZ] National Key R&D Program of China; 82271320 [ZZ] National Natural Science Foundation of China
- Contributed Indexing:
Keywords: Alzheimer’s disease; CD163; mild cognitive impairment; transcriptome; white-matter hyperintensities
- Accession Number:
EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
EC 1.2.1.3 (ALDH2 protein, human)
0 (Folate Receptor 2)
0 (FOLR2 protein, human)
0 (Transcription Factors)
0 (ZNF23 protein, human)
0 (CD163 antigen)
0 (Antigens, Differentiation, Myelomonocytic)
- Publication Date:
Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240228
- Publication Date:
20240229
- Accession Number:
PMC10888773
- Accession Number:
10.3390/ijms25042293
- Accession Number:
38396970
No Comments.