Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 04 2021
19 04 2021
Historique:
received:
29
04
2020
accepted:
03
03
2021
entrez:
20
4
2021
pubmed:
21
4
2021
medline:
11
5
2021
Statut:
epublish
Résumé
Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer's disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.
Identifiants
pubmed: 33875655
doi: 10.1038/s41467-021-22399-3
pii: 10.1038/s41467-021-22399-3
pmc: PMC8055900
doi:
Substances chimiques
Protein C Inhibitor
0
SERPINA5 protein, human
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2311Subventions
Organisme : NIA NIH HHS
ID : U01 AG057195
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051504
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062677
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054449
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034676
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Références
J Mol Neurosci. 2015 Sep;57(1):48-62
pubmed: 25982926
Acta Neuropathol. 1992;84(6):596-605
pubmed: 1281953
Acta Neuropathol Commun. 2016 Jun 13;4(1):58
pubmed: 27296779
Lancet Neurol. 2011 Mar;10(3):275-9
pubmed: 21349442
Nat Genet. 2011 May;43(5):436-41
pubmed: 21460841
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
J Neurosci. 2014 Dec 3;34(49):16247-55
pubmed: 25471565
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Oncogene. 2009 May 7;28(18):1971-81
pubmed: 19330022
J Biol Chem. 2009 Apr 24;284(17):11224-36
pubmed: 19240036
Blood. 2007 Jun 1;109(11):4769-76
pubmed: 17332248
J Neuropathol Exp Neurol. 2012 May;71(5):362-81
pubmed: 22487856
Nature. 1991 Feb 21;349(6311):704-6
pubmed: 1671712
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6923-8
pubmed: 11381127
Neurology. 1991 Apr;41(4):479-86
pubmed: 2011243
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Lancet Neurol. 2011 Sep;10(9):785-96
pubmed: 21802369
Eur J Biochem. 1996 May 15;238(1):88-96
pubmed: 8665956
BMC Bioinformatics. 2014 Jun 27;15:224
pubmed: 24972667
Blood Coagul Fibrinolysis. 1995 Jul;6(5):382-7
pubmed: 8589203
Nat Commun. 2018 Nov 1;9(1):4567
pubmed: 30385745
PLoS One. 2015 Nov 04;10(11):e0142122
pubmed: 26536597
Am J Pathol. 1987 Jan;126(1):81-91
pubmed: 2433949
J Cell Mol Med. 2018 Apr;22(4):2046-2054
pubmed: 29383875
Nat Genet. 2011 May;43(5):429-35
pubmed: 21460840
Nat Genet. 2009 Oct;41(10):1088-93
pubmed: 19734902
J Neurosci. 1999 Sep 1;19(17):7486-94
pubmed: 10460255
Sci Rep. 2018 Mar 9;8(1):4282
pubmed: 29523845
Diabetes Care. 2006 Jul;29(7):1518-22
pubmed: 16801572
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):510-4
pubmed: 24368848
Neurology. 2009 Sep 8;73(10):805-11
pubmed: 19738176
Neurobiol Aging. 2019 Feb;74:225-233
pubmed: 30497016
J Biol Chem. 1992 May 5;267(13):8789-94
pubmed: 1315738
BMC Genomics. 2012 Dec 10;13:689
pubmed: 23228338
Hum Mol Genet. 2015 Nov 1;24(21):6198-212
pubmed: 26276810
J Biol Chem. 1998 May 1;273(18):11281-7
pubmed: 9556620
Nat Rev Neurosci. 2007 Sep;8(9):663-72
pubmed: 17684513
Biochim Biophys Acta. 2010 Jun;1800(6):580-90
pubmed: 20230872
Biochem J. 2003 Jul 1;373(Pt 1):101-13
pubmed: 12656673
J Thromb Haemost. 2013 Jun;11 Suppl 1:254-64
pubmed: 23809129
Bioinformatics. 2012 Jun 1;28(11):1546-8
pubmed: 22513995
Cell Death Differ. 2001 Dec;8(12):1157-68
pubmed: 11753564
Alzheimers Dement. 2018 Mar;14(3):352-366
pubmed: 29107053
J Neuropathol Exp Neurol. 2012 Dec;71(12):1075-85
pubmed: 23147505
Nature. 2014 Dec 18;516(7531):349-54
pubmed: 25519132
JAMA Neurol. 2020 Feb 1;77(2):225-233
pubmed: 31657834
J Neuropathol Exp Neurol. 1999 Feb;58(2):188-97
pubmed: 10029101
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
J Biol Chem. 2001 Aug 24;276(34):31945-52
pubmed: 11395500
Acta Neuropathol. 2012 Nov;124(5):681-92
pubmed: 22968369
J Biol Chem. 1983 Jan 10;258(1):163-8
pubmed: 6294098
Sci Data. 2018 Sep 11;5:180185
pubmed: 30204156
JAMA. 2010 May 12;303(18):1832-40
pubmed: 20460622
Cell Rep. 2020 Jul 14;32(2):107908
pubmed: 32668255
Brain Res. 1989 Jan 16;477(1-2):90-9
pubmed: 2495152
Mol Pharmacol. 2002 Jun;61(6):1289-96
pubmed: 12021389
J Thromb Haemost. 2007 Jul;5(7):1486-92
pubmed: 17635698
Nat Commun. 2018 Oct 15;9(1):4273
pubmed: 30323170
Acta Neuropathol. 2018 Dec;136(6):873-885
pubmed: 30219939
JAMA. 2018 Apr 10;319(14):1429-1430
pubmed: 29566133
J Alzheimers Dis. 2015;48(3):647-65
pubmed: 26402107
Neuropathology. 2014 Dec;34(6):571-7
pubmed: 24612177
Sci Data. 2016 Oct 11;3:160089
pubmed: 27727239
Cell Signal. 2017 Jan;29:127-137
pubmed: 27989698
PLoS One. 2014 Jul 07;9(7):e101794
pubmed: 25000564
Alzheimers Res Ther. 2014 Nov 28;6(9):85
pubmed: 25435922
Mol Cell Biol. 2005 Aug;25(16):7193-202
pubmed: 16055728
Brain. 2016 May;139(Pt 5):1551-67
pubmed: 26962052
Biostatistics. 2012 Apr;13(2):204-16
pubmed: 22285995
Pharmacogenomics J. 2010 Oct;10(5):375-84
pubmed: 20029386
J Biol Chem. 2015 Jan 30;290(5):3081-91
pubmed: 25488662
J Cell Biol. 2007 Nov 19;179(4):793-804
pubmed: 18025309
Genetics. 2008 Jul;179(3):1373-88
pubmed: 18562658
JAMA Neurol. 2014 Apr;71(4):499-504
pubmed: 24514863
Toxicol Sci. 2019 Aug 1;170(2):357-373
pubmed: 31093665
Acta Neuropathol. 2014 Sep;128(3):411-21
pubmed: 24899141
Neurobiol Dis. 2020 Sep;143:104976
pubmed: 32565066
Acta Neuropathol. 2012 Jan;123(1):1-11
pubmed: 22101365
Thromb Haemost. 2014 Jan;111(1):41-52
pubmed: 24136361
Brain. 2015 May;138(Pt 5):1370-81
pubmed: 25805643
Nat Genet. 2009 Oct;41(10):1094-9
pubmed: 19734903
Nature. 1995 Jun 29;375(6534):754-60
pubmed: 7596406
Annu Rev Neurosci. 2011;34:185-204
pubmed: 21456963
Neurology. 2002 Jun 25;58(12):1791-800
pubmed: 12084879
J Biol Chem. 2008 Oct 31;283(44):29615-9
pubmed: 18650430
PLoS One. 2013 Nov 22;8(11):e81925
pubmed: 24278466
Gynecol Oncol. 2010 Mar;116(3):399-403
pubmed: 20022094
Alzheimers Dement. 2019 May;15(5):635-643
pubmed: 30792090
Biochem Biophys Res Commun. 2013 Oct 25;440(3):431-6
pubmed: 24076122
BMC Mol Biol. 2006 Jan 31;7:3
pubmed: 16448564
Alzheimers Res Ther. 2012 Aug 20;4(4):34
pubmed: 22906081
J Clin Invest. 1980 Nov;66(5):1186-9
pubmed: 6253526
Mol Carcinog. 2010 Feb;49(2):105-13
pubmed: 19908242
J Alzheimers Dis. 2018;66(2):681-691
pubmed: 30320571
Front Pharmacol. 2018 Feb 07;9:63
pubmed: 29467657