TREM2-induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology.
Alzheimer's disease
TREM2
microglia
phosphatidylserine
resilience
synapses
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
18
05
2022
accepted:
16
06
2022
pubmed:
12
7
2022
medline:
17
1
2023
entrez:
11
7
2022
Statut:
ppublish
Résumé
The existence of individuals who remain cognitively intact despite presenting histopathological signs of Alzheimer's disease (AD), here referred to as "Nondemented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. Exposed phosphatidylserine (ePS) represents a neuronal "eat-me" signal involved in microglial-mediated phagocytosis of damaged synapses. A possible mediator of this process is TREM2, a microglial surface receptor activated by ligands including PS. Based on TREM2 role in the scavenging function of microglia, we hypothesize that an efficient microglial phagocytosis of damaged synapses underlies synaptic resilience in NDAN, thus protecting from memory deficits. Using immunofluorescence microscopy, we performed a comparative study of human post-mortem frontal cortices of aged-matched, AD and NDAN individuals. We studied the distribution of activated microglia (IBA1, IBA1
Identifiants
pubmed: 35816404
doi: 10.1111/bpa.13108
pmc: PMC9836373
doi:
Substances chimiques
TREM2 protein, human
0
Membrane Glycoproteins
0
Receptors, Immunologic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13108Subventions
Organisme : NIA NIH HHS
ID : P30 AG066518
Pays : United States
Organisme : Excellence Departments, MIUR
ID : L.232/2016
Organisme : NIA NIH HHS
ID : RF1 AG060718
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060718
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG069433
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008017
Pays : United States
Organisme : Robert J. and Helen C. Kleberg Foundation
Informations de copyright
© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
Références
Front Aging Neurosci. 2018 Jul 09;10:202
pubmed: 30038567
J Neuropathol Exp Neurol. 2017 Feb 08;76(2):109-125
pubmed: 28177496
Alzheimers Dement. 2022 Apr;18(4):700-789
pubmed: 35289055
N Engl J Med. 2013 Jan 10;368(2):117-27
pubmed: 23150934
Sci Rep. 2016 Jun 14;6:27812
pubmed: 27298190
Mol Neurodegener. 2012 May 28;7:23
pubmed: 22640423
Sci Rep. 2019 May 17;9(1):7508
pubmed: 31101881
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Cell. 2017 Jun 15;169(7):1276-1290.e17
pubmed: 28602351
J Alzheimers Dis. 2018;65(2):659-682
pubmed: 30103319
Front Cell Neurosci. 2018 Aug 06;12:206
pubmed: 30127720
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Nat Rev Neurol. 2018 Nov;14(11):667-675
pubmed: 30266932
Acta Neuropathol. 2016 Aug;132(2):235-256
pubmed: 26993139
Cell. 2018 May 17;173(5):1073-1081
pubmed: 29775591
EMBO J. 2020 Aug 17;39(16):e105380
pubmed: 32657463
Nat Med. 2020 Jan;26(1):131-142
pubmed: 31932797
Exp Neurol. 2018 Apr;302:205-213
pubmed: 29407460
Inflammation. 2018 Jun;41(3):811-823
pubmed: 29362997
Trends Neurosci. 2019 May;42(5):310-322
pubmed: 31006494
Immunity. 2018 May 15;48(5):979-991.e8
pubmed: 29752066
Biol Psychiatry. 2018 Feb 15;83(4):347-357
pubmed: 28434655
Mol Neurobiol. 2020 May;57(5):2232-2243
pubmed: 31997075
Mol Psychiatry. 2018 Feb;23(2):177-198
pubmed: 29230021
Nat Immunol. 2018 Oct;19(10):1048-1058
pubmed: 30250185
J Neurosci. 2021 Jan 20;41(3):538-554
pubmed: 33239403
Hum Mol Genet. 2020 Nov 25;29(19):3224-3248
pubmed: 32959884
Neuron. 2018 Mar 7;97(5):1032-1048.e5
pubmed: 29518357
Mol Neurodegener. 2018 Mar 27;13(1):15
pubmed: 29587871
J Cell Biol. 2018 Feb 5;217(2):459-472
pubmed: 29196460
Mol Neurodegener. 2018 Dec 20;13(1):66
pubmed: 30572908
Neurochem Int. 2004 Feb;44(3):125-31
pubmed: 14568554
Sci Rep. 2019 Apr 25;9(1):6555
pubmed: 31024073
N Engl J Med. 2013 Jan 10;368(2):107-16
pubmed: 23150908
Cell Mol Life Sci. 2022 Apr 4;79(4):222
pubmed: 35377002
J Neurosci Methods. 2016 Mar 1;261:128-34
pubmed: 26774027
Brain Pathol. 2023 Jan;33(1):e13108
pubmed: 35816404
J Alzheimers Dis. 2020;78(4):1661-1678
pubmed: 33185603
Biochem Biophys Res Commun. 1996 Jul 25;224(3):855-62
pubmed: 8713135
Int J Mol Sci. 2018 Jan 22;19(1):
pubmed: 29361745
Glia. 2019 May;67(5):844-856
pubmed: 30588668
Front Cell Neurosci. 2019 Oct 10;13:457
pubmed: 31649511
Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6303-6308
pubmed: 29844190