Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.
Alzheimer’s
Astrocyte
Glia
Immune
NODDI
Neurites
Normal Aging
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
08
12
2022
revised:
14
06
2023
accepted:
27
06
2023
pmc-release:
01
10
2024
medline:
4
9
2023
pubmed:
3
7
2023
entrez:
2
7
2023
Statut:
ppublish
Résumé
Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aβ42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.
Sections du résumé
BACKGROUND
Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life.
METHODS
We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109).
RESULTS
When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aβ42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females.
DISCUSSION
This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.
Identifiants
pubmed: 37394144
pii: S0889-1591(23)00169-1
doi: 10.1016/j.bbi.2023.06.026
pmc: PMC10584366
mid: NIHMS1918615
pii:
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-135Subventions
Organisme : NIH HHS
ID : S10 OD018435
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058772
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG072153
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG080427
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Biomed Inform. 2009 Apr;42(2):377-81
pubmed: 18929686
J Stat Softw. 2010;33(1):1-22
pubmed: 20808728
Nat Rev Neurol. 2010 Feb;6(2):67-77
pubmed: 20139996
Br J Pharmacol. 2019 Sep;176(18):3585-3598
pubmed: 30636042
JAMA Neurol. 2021 Dec 1;78(12):1471-1483
pubmed: 34661615
J Neuroinflammation. 2011 Mar 25;8:26
pubmed: 21439035
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1896-E1905
pubmed: 29437957
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
Trends Neurosci. 1999 May;22(5):208-15
pubmed: 10322493
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Neuroscience. 2013 Oct 22;251:21-32
pubmed: 23069756
Eur J Neurosci. 1998 Apr;10(4):1261-9
pubmed: 9749780
Alzheimers Dement. 2022 Jun;18(6):1141-1154
pubmed: 34494715
Neurobiol Aging. 2021 Jul;103:68-77
pubmed: 33845398
Mol Neurodegener. 2019 Jun 7;14(1):21
pubmed: 31174557
Nat Neurosci. 2019 Feb;22(2):154-166
pubmed: 30664773
Biol Psychiatry. 2022 Jan 1;91(1):72-80
pubmed: 33715827
Trends Mol Med. 2019 Sep;25(9):741-749
pubmed: 31171460
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
J Alzheimers Dis. 2018;63(2):577-590
pubmed: 29660934
Alzheimers Dement. 2011 May;7(3):270-9
pubmed: 21514249
Cereb Cortex. 2020 May 14;30(5):2948-2960
pubmed: 31833550
Brain. 2021 Dec 16;144(11):3505-3516
pubmed: 34259835
Nat Med. 2022 Sep;28(9):1797-1801
pubmed: 35953717
Alzheimers Dement. 2019 Jun;15(6):776-787
pubmed: 31047856
Neurodegener Dis. 2010;7(1-3):38-41
pubmed: 20160456
Neuroimage. 2016 Jan 15;125:739-744
pubmed: 26505297
Int J Mol Sci. 2021 Feb 20;22(4):
pubmed: 33672696
Neuroimage. 2003 Oct;20(2):870-88
pubmed: 14568458
Neurosci Biobehav Rev. 2016 Sep;68:547-562
pubmed: 27328788
J Alzheimers Dis. 2018;62(1):385-397
pubmed: 29439331
Brain. 2007 Mar;130(Pt 3):720-30
pubmed: 17293358
Alzheimers Dement. 2022 Apr;18(4):645-653
pubmed: 34160128
Neuroimage. 2006 Jul 1;31(3):968-80
pubmed: 16530430
Mol Neurodegener. 2016 Jan 12;11:2
pubmed: 26754117
Mol Interv. 2001 Apr;1(1):22-9
pubmed: 14993335
Brain. 2022 Oct 21;145(10):3536-3545
pubmed: 35869598
Tohoku J Exp Med. 1994 Nov;174(3):295-303
pubmed: 7539162
Neuroimage. 2004;23 Suppl 1:S208-19
pubmed: 15501092
J Neurosci. 2002 Jan 1;22(1):183-92
pubmed: 11756501
Neuroimage Clin. 2016 May 30;11:802-812
pubmed: 28050342
Ann Neurol. 2002 Aug;52(2):168-74
pubmed: 12210786
Neuroimage. 2018 Nov 15;182:488-499
pubmed: 29448073
Neuroimage. 2012 Jul 16;61(4):1000-16
pubmed: 22484410
Acta Neuropathol. 2015 Jul;130(1):1-19
pubmed: 26063233
Alzheimers Dement. 2022 Dec;18(12):2669-2686
pubmed: 35908251
Cold Spring Harb Perspect Biol. 2014 Nov 07;7(2):a020420
pubmed: 25380660
J Clin Exp Neuropsychol. 2019 Dec;41(10):1048-1059
pubmed: 31370773
J Alzheimers Dis. 2019;67(2):481-488
pubmed: 30594925
Mol Neurobiol. 2019 Jan;56(1):406-434
pubmed: 29705945
Brain Behav Immun. 2012 Jan;26(1):103-8
pubmed: 21843630
Neuroimage. 2016 Nov 1;141:556-572
pubmed: 27393418
Nat Rev Neurol. 2021 Nov;17(11):689-701
pubmed: 34522039
Neuropathol Appl Neurobiol. 2017 Jun;43(4):281-298
pubmed: 27442752
PLoS One. 2019 Sep 25;14(9):e0217118
pubmed: 31553719
Alzheimers Dement. 2020 Apr;16(4):681-695
pubmed: 31879236
Alzheimers Dement. 2022 Jan;18(1):65-76
pubmed: 33984184
Front Aging Neurosci. 2019 Feb 13;11:25
pubmed: 30814948
Mol Psychiatry. 2022 Oct;27(10):4314-4322
pubmed: 35768637
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
JAMA Netw Open. 2018 Oct 5;1(6):e183597
pubmed: 30646251
Alzheimers Dement. 2022 Jul 19;:
pubmed: 35852967
Mol Neurodegener. 2019 Aug 2;14(1):32
pubmed: 31375134
Alzheimers Res Ther. 2022 Aug 3;14(1):106
pubmed: 35922871
Ageing Res Rev. 2021 Jul;68:101335
pubmed: 33812051
PLoS One. 2012;7(1):e30525
pubmed: 22303443
Cereb Cortex. 1991 Jan-Feb;1(1):103-16
pubmed: 1822725
Brain. 2022 Oct 21;145(10):3341-3342
pubmed: 36052679