Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer's disease: a randomized trial.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 01 2022
25 01 2022
Historique:
received:
01
09
2021
accepted:
05
01
2022
entrez:
26
1
2022
pubmed:
27
1
2022
medline:
8
3
2022
Statut:
epublish
Résumé
Intranasal insulin (INI) has shown promise as a treatment for Alzheimer's disease (AD) in pilot clinical trials. In a recent phase 2 trial, participants with mild cognitive impairment (MCI) or AD who were treated with INI with one of two delivery devices showed improved cerebral spinal fluid (CSF) biomarker profiles and slower symptom progression compared with placebo. In the cohort which showed benefit, we measured changes in CSF markers of inflammation, immune function and vascular integrity and assessed their relationship with changes in cognition, brain volume, and CSF amyloid and tau concentrations. The insulin-treated group had increased CSF interferon-γ (p = 0.032) and eotaxin (p = 0.049), and reduced interleukin-6 (p = 0.048) over the 12 month trial compared to placebo. Trends were observed for increased CSF macrophage-derived chemokine for the placebo group (p = 0.083), and increased interleukin-2 in the insulin-treated group (p = 0.093). Insulin-treated and placebo groups showed strikingly different patterns of associations between changes in CSF immune/inflammatory/vascular markers and changes in cognition, brain volume, and amyloid and tau concentrations. In summary, INI treatment altered the typical progression of markers of inflammation and immune function seen in AD, suggesting that INI may promote a compensatory immune response associated with therapeutic benefit.
Identifiants
pubmed: 35079029
doi: 10.1038/s41598-022-05165-3
pii: 10.1038/s41598-022-05165-3
pmc: PMC8789895
doi:
Substances chimiques
Biomarkers
0
Insulin
0
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1346Subventions
Organisme : NIA NIH HHS
ID : P30 AG072947
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG041845
Pays : United States
Organisme : NIA NIH HHS
ID : RF1AG041845
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Neuroimage. 2012 Feb 15;59(4):3774-83
pubmed: 22119648
Brain Res Dev Brain Res. 2002 Jun 30;136(2):111-21
pubmed: 12101028
N Engl J Med. 2011 Dec 1;365(22):2067-77
pubmed: 22129253
Lancet Neurol. 2013 Feb;12(2):207-16
pubmed: 23332364
Curr Neurol Neurosci Rep. 2013 Dec;13(12):415
pubmed: 24190781
Neuroimage Clin. 2016 May 30;11:802-812
pubmed: 28050342
Int J Biol Sci. 2012;8(9):1254-66
pubmed: 23136554
J Biol Chem. 1984 Oct 10;259(19):11672-5
pubmed: 6384211
J Clin Med. 2019 May 10;8(5):
pubmed: 31083442
Curr Alzheimer Res. 2015;12(7):684-93
pubmed: 26159205
Neurobiol Dis. 2015 Oct;82:593-606
pubmed: 26311408
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110343
pubmed: 33961966
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Front Immunol. 2021 Feb 19;11:587229
pubmed: 33679687
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2264-9
pubmed: 23335631
Front Neurol. 2012 Apr 25;3:64
pubmed: 22539931
Alzheimers Res Ther. 2017 Jun 6;9(1):38
pubmed: 28587659
J Recept Signal Transduct Res. 2017 Aug;37(4):416-421
pubmed: 28279120
Nat Commun. 2016 Jun 21;7:11934
pubmed: 27327500
Biomol Concepts. 2019 Feb 22;10(1):11-24
pubmed: 30827953
J Neurol Neurosurg Psychiatry. 2019 May;90(5):590-598
pubmed: 30630955
Immunity. 2018 Jul 17;49(1):164-177.e6
pubmed: 29958802
Alzheimers Dement. 2021 Jun 23;:
pubmed: 34160128
Acta Neuropathol. 2016 May;131(5):753-73
pubmed: 26932603
Nat Commun. 2018 Nov 2;9(1):4593
pubmed: 30389931
Alzheimer Dis Assoc Disord. 2010 Jul-Sep;24(3):284-90
pubmed: 20683186
Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S13-21
pubmed: 9236948
Alzheimers Dement (N Y). 2018 Sep 06;4:575-590
pubmed: 30406177
Lancet Neurol. 2020 Sep;19(9):758-766
pubmed: 32730766
J Prev Alzheimers Dis. 2021;8(3):240-248
pubmed: 34101779
Am J Manag Care. 2020 Aug;26(8 Suppl):S177-S183
pubmed: 32840331
Clin Immunol. 2018 Apr;189:29-33
pubmed: 27664933
Front Neurosci. 2020 Jan 21;13:1436
pubmed: 32038141
J Biol Chem. 2018 Aug 10;293(32):12620-12633
pubmed: 29599291
PLoS One. 2012;7(7):e39794
pubmed: 22815714
FASEB J. 2008 Aug;22(8):2843-52
pubmed: 18390924
Biol Psychiatry. 2010 Nov 15;68(10):930-41
pubmed: 20692646
Sci Rep. 2017 Aug 29;7(1):9766
pubmed: 28852028
Transl Stroke Res. 2017 Dec;8(6):578-584
pubmed: 28634890
J Neuroinflammation. 2017 Jan 3;14(1):1
pubmed: 28086917
J Clin Exp Neuropsychol. 1992 Mar;14(2):253-67
pubmed: 1572948
Neuroscience. 2019 May 1;405:24-34
pubmed: 29427657
J Neuroimmunol. 2007 Feb;183(1-2):1-6
pubmed: 17188367
Brain. 2017 Mar 1;140(3):826-842
pubmed: 28003243
Autoimmun Rev. 2020 Oct;19(10):102645
pubmed: 32801037
J Alzheimers Dis. 2005 Feb;7(1):45-61
pubmed: 15750214
J Neuroimmune Pharmacol. 2017 Jun;12(2):233-248
pubmed: 27726055
PLoS One. 2014 Apr 23;9(4):e95995
pubmed: 24760020
J Clin Neurol. 2008 Jun;4(2):84-8
pubmed: 19513308
Brain Res Rev. 2011 Jun 24;67(1-2):157-83
pubmed: 21238488
Nat Rev Immunol. 2015 May;15(5):283-94
pubmed: 25882245
JAMA Neurol. 2020 Sep 1;77(9):1099-1109
pubmed: 32568367
Neurology. 2009 Jun 2;72(22):1906-13
pubmed: 19487648
Neurobiol Aging. 2019 Apr;76:125-132
pubmed: 30711675
Neurology. 2018 Mar 27;90(13):e1150-e1157
pubmed: 29476033
Ann Clin Transl Neurol. 2019 Mar 29;6(5):863-872
pubmed: 31139684
Cell Metab. 2018 Jun 05;27(6):1176-1199
pubmed: 29874566
Sci Rep. 2019 Oct 1;9(1):14102
pubmed: 31575996
Curr Opin Lipidol. 2019 Aug;30(4):320-325
pubmed: 31135596
ScientificWorldJournal. 2009 Jul 04;9:557-63
pubmed: 19578713
Neurol Neuroimmunol Neuroinflamm. 2015 Aug 06;2(5):e138
pubmed: 26280014
JAMA. 2021 May 4;325(17):1717-1718
pubmed: 33783469
Dement Geriatr Cogn Dis Extra. 2015 Nov 24;5(3):424-34
pubmed: 26675645
Nat Rev Neurol. 2018 Mar;14(3):168-181
pubmed: 29377010
Int J Alzheimers Dis. 2010 Jun 23;2010:
pubmed: 20721349
Dement Geriatr Cogn Disord. 2009;28(4):281-7
pubmed: 19828948
Vasc Endovascular Surg. 2008 Dec-2009 Jan;42(6):517-30
pubmed: 18799497
Alzheimers Dement. 2015 Jun;11(6):710-7
pubmed: 25510382
Front Aging Neurosci. 2021 May 28;13:670115
pubmed: 34122046