Microglia and its Genetics in Alzheimer's Disease.
AD risk genes
APOE
Alzheimer's Disease
GWAS.
microglia
neuroinflammation
Journal
Current Alzheimer research
ISSN: 1875-5828
Titre abrégé: Curr Alzheimer Res
Pays: United Arab Emirates
ID NLM: 101208441
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
03
2021
revised:
30
06
2021
accepted:
03
07
2021
pubmed:
10
11
2021
medline:
2
4
2022
entrez:
9
11
2021
Statut:
ppublish
Résumé
Alzheimer's Disease (AD) is the most prevalent form of dementia across the world. While its discovery and pathological manifestations are centered on protein aggregations of amyloid- beta (Aβ) and hyperphosphorylated tau protein, neuroinflammation has emerged in the last decade as a main component of the disease in terms of both pathogenesis and progression. As the main innate immune cell type in the central nervous system (CNS), microglia play a very important role in regulating neuroinflammation, which occurs commonly in neurodegenerative conditions, including AD. Under inflammatory response, microglia undergo morphological changes and status transition from homeostatic to activated forms. Different microglia subtypes displaying distinct genetic profiles have been identified in AD, and these signatures often link to AD risk genes identified from the genome-wide association studies (GWAS), such as APOE and TREM2. Furthermore, many AD risk genes are highly enriched in microglia and specifically influence the functions of microglia in pathogenesis, e.g. releasing inflammatory cytokines and clearing Aβ. Therefore, building up a landscape of these risk genes in microglia, based on current preclinical studies and in the context of their pathogenic or protective effects, would largely help us to understand the complex etiology of AD and provide new insight into the unmet need for effective treatment.
Identifiants
pubmed: 34749609
pii: CAR-EPUB-118734
doi: 10.2174/1567205018666211105140732
pmc: PMC9790807
mid: NIHMS1856914
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
676-688Subventions
Organisme : NIA NIH HHS
ID : R21 AG066090
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061288
Pays : United States
Organisme : NINDS NIH HHS
ID : RF1 NS122060
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS110687
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG063287
Pays : United States
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Neurobiol Stress. 2018 May 19;9:9-21
pubmed: 29992181
J Neurosci. 2012 Oct 24;32(43):15112-23
pubmed: 23100432
J Alzheimers Dis. 2016 Sep 6;54(2):569-84
pubmed: 27472885
Neuron. 2013 May 22;78(4):631-43
pubmed: 23623698
Mol Neurodegener. 2019 Jan 10;14(1):1
pubmed: 30630532
Nat Genet. 2011 May;43(5):436-41
pubmed: 21460841
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Neurology. 2013 May 7;80(19):1778-83
pubmed: 23390181
Alzheimers Dement. 2020 Mar 10;:
pubmed: 32157811
Cell Commun Signal. 2015 Oct 01;13:41
pubmed: 26428302
Hum Genet. 2018 Apr;137(4):305-314
pubmed: 29675612
Neurobiol Dis. 2005 Mar;18(2):390-8
pubmed: 15686968
J Neurosci. 2016 Mar 30;36(13):3848-59
pubmed: 27030769
J Neuroinflammation. 2014 Jul 25;11:127
pubmed: 25062954
Acta Neuropathol. 2014 Apr;127(4):495-505
pubmed: 24407428
Cell. 2017 Jun 15;169(7):1276-1290.e17
pubmed: 28602351
Mol Psychiatry. 2020 Feb;25(2):351-367
pubmed: 31772305
Nature. 2020 May;581(7806):71-76
pubmed: 32376954
Alzheimers Dement (N Y). 2020 Jul 16;6(1):e12050
pubmed: 32695874
Lancet Neurol. 2019 Jan;18(1):88-106
pubmed: 30497964
Nat Neurosci. 2007 Dec;10(12):1544-53
pubmed: 18026096
Nat Rev Neurol. 2018 Nov;14(11):667-675
pubmed: 30266932
Neuron. 2018 Jun 27;98(6):1141-1154.e7
pubmed: 29861287
J Neurosci. 2010 Dec 15;30(50):17091-101
pubmed: 21159979
Prog Neurobiol. 2017 Feb - Mar;149-150:1-20
pubmed: 28143732
Res Rep Biochem. 2015;5:89-100
pubmed: 26478868
Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1541-5
pubmed: 1996355
Nat Genet. 2011 May;43(5):429-35
pubmed: 21460840
Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1807-16
pubmed: 23620513
Nature. 2019 Nov;575(7784):669-673
pubmed: 31748742
Nat Rev Neurol. 2011 Mar;7(3):137-52
pubmed: 21304480
Immunity. 2019 Jan 15;50(1):253-271.e6
pubmed: 30471926
Cell. 2018 Aug 9;174(4):999-1014.e22
pubmed: 30096314
Cell Rep. 2019 Apr 23;27(4):1293-1306.e6
pubmed: 31018141
Nature. 2017 Sep 28;549(7673):523-527
pubmed: 28959956
J Neuroinflammation. 2015 Nov 04;12:203
pubmed: 26538310
Nat Neurosci. 2018 Jul;21(7):897-899
pubmed: 29942037
J Alzheimers Dis. 2019;70(1):17-23
pubmed: 31127786
Am J Hum Genet. 2008 Nov;83(5):623-32
pubmed: 18976728
Hum Mol Genet. 2014 May 15;23(10):2729-36
pubmed: 24381305
J Neuroinflammation. 2020 Mar 19;17(1):88
pubmed: 32192522
Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23790-23796
pubmed: 31690660
Nat Neurosci. 2015 Jul;18(7):978-87
pubmed: 26005850
J Exp Med. 2012 Nov 19;209(12):2149-56
pubmed: 23129750
Nature. 2013 Jan 31;493(7434):674-8
pubmed: 23254930
FASEB J. 2001 May;15(7):1209-11
pubmed: 11344090
Glia. 2016 Oct;64(10):1710-32
pubmed: 27100611
Nat Rev Neurol. 2017 Jul;13(7):420-433
pubmed: 28524175
Nature. 2019 Jun;570(7761):332-337
pubmed: 31042697
Brain. 2017 Sep 1;140(9):2273-2285
pubmed: 29050380
J Exp Med. 2016 May 2;213(5):667-75
pubmed: 27091843
Nat Rev Neurol. 2015 Jan;11(1):56-64
pubmed: 25385337
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):12011-6
pubmed: 20547867
J Neurosci. 2020 Feb 26;40(9):1956-1974
pubmed: 31980586
Cold Spring Harb Perspect Med. 2012 Oct 01;2(10):
pubmed: 23028126
Neuron. 2014 Feb 19;81(4):740-54
pubmed: 24559670
Brain. 2015 May;138(Pt 5):1138-59
pubmed: 25823474
Immunity. 2017 Sep 19;47(3):566-581.e9
pubmed: 28930663
Neuron. 2020 Jun 3;106(5):727-742.e6
pubmed: 32199103
Nat Neurosci. 2018 Oct;21(10):1359-1369
pubmed: 30258234
Nat Rev Neurol. 2019 Sep;15(9):501-518
pubmed: 31367008
Neuron. 2016 May 18;90(4):724-39
pubmed: 27196974
Cancer Res. 2002 Apr 15;62(8):2215-9
pubmed: 11956071
Trends Biochem Sci. 2016 Dec;41(12):1012-1021
pubmed: 27669650
Nat Genet. 2017 Sep;49(9):1373-1384
pubmed: 28714976
Nat Rev Neurol. 2013 Feb;9(2):106-18
pubmed: 23296339
Nat Commun. 2015 Jan 29;6:6176
pubmed: 25630253
Mol Neurodegener. 2017 May 26;12(1):43
pubmed: 28549481
Hum Genet. 2012 Jul;131(7):1245-9
pubmed: 22382309
J Neuroimmunol. 2020 Apr 15;341:577185
pubmed: 32045774
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18700-5
pubmed: 16344478
Lancet Neurol. 2015 Apr;14(4):388-405
pubmed: 25792098
Brain Behav Immun. 2013 Aug;32:70-85
pubmed: 23454862
J Cell Biol. 2018 Feb 5;217(2):459-472
pubmed: 29196460
EMBO Mol Med. 2016 May 02;8(5):466-76
pubmed: 26941262
Science. 2010 Nov 5;330(6005):841-5
pubmed: 20966214
J Clin Invest. 2013 Jan;123(1):224-35
pubmed: 23202730
Front Neurol. 2020 Sep 18;11:570711
pubmed: 33071950
Curr Opin Neurobiol. 2020 Apr;61:40-48
pubmed: 31863938
J Neuroinflammation. 2014 Jun 03;11:98
pubmed: 24889886
Cold Spring Harb Perspect Biol. 2015 Jul 01;7(8):a020537
pubmed: 26134003
J Exp Med. 2015 Mar 9;212(3):287-95
pubmed: 25732305
Gerontology. 2019;65(4):323-331
pubmed: 30541012
Transl Psychiatry. 2019 Jan 31;9(1):55
pubmed: 30705288
Front Cell Neurosci. 2017 Mar 09;11:63
pubmed: 28337127
J Mol Med (Berl). 2009 Jul;87(7):697-701
pubmed: 19390836
Immunity. 2019 Apr 16;50(4):955-974
pubmed: 30995509
Neuron. 1997 Oct;19(4):939-45
pubmed: 9354339
Science. 2017 Jun 23;356(6344):
pubmed: 28546318
Alzheimers Res Ther. 2019 Feb 2;11(1):16
pubmed: 30711010
Nat Rev Neurol. 2010 Apr;6(4):193-201
pubmed: 20234358
Brain Res Dev Brain Res. 1999 Nov 18;117(2):145-52
pubmed: 10567732
Glia. 2016 May;64(5):826-39
pubmed: 26847266
N Engl J Med. 2013 Jan 10;368(2):107-16
pubmed: 23150908
Nat Neurosci. 2011 Jul 31;14(9):1142-9
pubmed: 21804537
Nat Neurosci. 2019 Feb;22(2):191-204
pubmed: 30617257
Alzheimers Dement. 2011 Jul;7(4):e124-9
pubmed: 21784344
Sci Transl Med. 2019 Aug 14;11(505):
pubmed: 31413141
Front Immunol. 2019 Oct 25;10:2538
pubmed: 31749805
J Neurosci. 2013 Aug 14;33(33):13320-5
pubmed: 23946390
Front Cell Neurosci. 2013 Apr 17;7:45
pubmed: 23616747
Ann Neurol. 2010 Dec;68(6):934-43
pubmed: 21061402
Mol Neurobiol. 2015 Apr;51(2):753-65
pubmed: 24794147
Neuron. 2019 Sep 4;103(5):820-835.e7
pubmed: 31301936
Nat Rev Immunol. 2019 Aug;19(8):477-489
pubmed: 31036962
Mol Neurobiol. 2015 Aug;52(1):414-21
pubmed: 25186233
Nat Neurosci. 2014 May;17(5):661-3
pubmed: 24728269
J Neuroinflammation. 2016 Jan 13;13:9
pubmed: 26757726
Acta Neuropathol. 2013 Jun;125(6):861-78
pubmed: 23589030
CNS Drugs. 2016 Sep;30(9):773-89
pubmed: 27328687
N Engl J Med. 2013 Jan 10;368(2):117-27
pubmed: 23150934
Nature. 2012 May 16;485(7399):512-6
pubmed: 22622580
Neurobiol Aging. 2017 Jul;55:115-122
pubmed: 28434692
Front Mol Neurosci. 2018 Sep 04;11:320
pubmed: 30233319
Mol Neurodegener. 2018 Oct 11;13(1):53
pubmed: 30326945
J Neuroimmunol. 1989 Oct;24(3):173-82
pubmed: 2808689
Nat Med. 2017 Sep 8;23(9):1018-1027
pubmed: 28886007
Cell. 2019 Oct 3;179(2):312-339
pubmed: 31564456
PLoS One. 2012;7(11):e50976
pubmed: 23226438
Nat Genet. 2019 Mar;51(3):414-430
pubmed: 30820047
Neuron. 2016 Jul 20;91(2):328-40
pubmed: 27477018
Cell Rep. 2020 Jun 30;31(13):107843
pubmed: 32610143
Front Hum Neurosci. 2019 Nov 05;13:387
pubmed: 31749691
Alzheimers Dement. 2017 Apr;13(4):381-387
pubmed: 27520774
Cell. 2017 Jan 26;168(3):427-441.e21
pubmed: 28111074
J Clin Invest. 2018 May 1;128(5):2144-2155
pubmed: 29600961
Cell Rep. 2020 Feb 4;30(5):1271-1281
pubmed: 32023447
J Hist Neurosci. 2002 Dec;11(4):325-74
pubmed: 12557654
J Biol Chem. 2013 May 24;288(21):15154-66
pubmed: 23580652
J Alzheimers Dis. 2013;35(4):697-713
pubmed: 23481688
Genome Med. 2011 May 31;3(5):33
pubmed: 21627779
Acta Neuropathol. 2019 Aug;138(2):187-199
pubmed: 30949760
J Biol Chem. 2015 Oct 23;290(43):26043-50
pubmed: 26374899
J Neuroinflammation. 2020 Aug 14;17(1):238
pubmed: 32795308
Acta Neuropathol. 2020 Jun;139(6):1025-1044
pubmed: 32166339
Int J Mol Sci. 2019 Jul 06;20(13):
pubmed: 31284572
EMBO J. 2019 Sep 2;38(17):e101997
pubmed: 31373067
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51
pubmed: 16567625
Radiology. 2003 Dec;229(3):691-6
pubmed: 14657306
Nat Genet. 2009 Oct;41(10):1094-9
pubmed: 19734903
Adv Exp Med Biol. 2019;1118:83-116
pubmed: 30747419
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2018-22
pubmed: 19164761
Cell. 2013 Apr 25;153(3):707-20
pubmed: 23622250
Nat Rev Immunol. 2007 Apr;7(4):255-66
pubmed: 17380156
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8788-E8797
pubmed: 28904096
Prog Neurobiol. 2017 Aug;155:57-75
pubmed: 27107797
Neuron. 2017 Dec 6;96(5):1024-1032.e3
pubmed: 29216449
Nat Neurosci. 2017 Aug;20(8):1162-1171
pubmed: 28671693