Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia.
Alzheimer’s disease
biomarkers
pathologic angiogenesis
vascular dementia
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
12
5
2020
medline:
11
5
2021
entrez:
12
5
2020
Statut:
ppublish
Résumé
Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia. To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults. Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-β peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity. Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities. We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.
Sections du résumé
BACKGROUND
Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia.
OBJECTIVE
To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults.
METHODS
Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-β peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity.
RESULTS
Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities.
CONCLUSION
We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.
Identifiants
pubmed: 32390626
pii: JAD191293
doi: 10.3233/JAD-191293
pmc: PMC8351220
mid: NIHMS1729651
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
959-969Subventions
Organisme : NIA NIH HHS
ID : R01 AG019771
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG051932
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001108
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG049050
Pays : United States
Références
J Alzheimers Dis. 2010;19(4):1231-40
pubmed: 20308789
Alzheimers Dement (Amst). 2017 Sep 23;9:57-66
pubmed: 29159268
J Am Coll Cardiol. 2006 Oct 17;48(8):1579-87
pubmed: 17045891
Eur J Neurosci. 2012 Jun;35(12):1917-37
pubmed: 22708603
Nature. 2011 May 19;473(7347):298-307
pubmed: 21593862
J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):343-349
pubmed: 29534173
Clin Sci (Lond). 2018 Feb 14;132(3):399-418
pubmed: 29444850
Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):1045-53
pubmed: 22282356
PLoS One. 2017 Sep 14;12(9):e0184895
pubmed: 28910385
Stem Cells Transl Med. 2017 May;6(5):1316-1320
pubmed: 28296182
JAMA Neurol. 2015 May;72(5):520-9
pubmed: 25751166
Lancet Neurol. 2004 Mar;3(3):184-90
pubmed: 14980533
Arch Pathol Lab Med. 2006 Dec;130(12):1850-8
pubmed: 17149963
Alzheimers Res Ther. 2018 Jun 23;10(1):58
pubmed: 29933741
Cardiovasc Res. 2010 Jul 1;87(1):12-21
pubmed: 20427336
J Alzheimers Dis. 2016;51(4):1145-55
pubmed: 26923008
Am J Med Genet B Neuropsychiatr Genet. 2017 Jan;174(1):93-112
pubmed: 26879907
J Alzheimers Dis. 2015;43(1):1-17
pubmed: 25061056
Alzheimers Dement. 2015 Jan;11(1):1-15.e1-4
pubmed: 25443857
Circ Res. 2012 Apr 27;110(9):1252-64
pubmed: 22539758
J Immunol Methods. 2000 Sep 21;243(1-2):77-97
pubmed: 10986408
Nat Immunol. 2006 Jul;7(7):681-5
pubmed: 16785881
Am J Pathol. 2012 Aug;181(2):376-9
pubmed: 22749677
Eur Heart J. 2003 Apr;24(7):586-603
pubmed: 12657217
Aging (Albany NY). 2018 Dec 16;11(1):3-4
pubmed: 30554190
Angiogenesis. 2013 Oct;16(4):953-62
pubmed: 23877751
Lancet. 2003 Feb 15;361(9357):605-8
pubmed: 12598159
Nature. 2005 Dec 15;438(7070):932-6
pubmed: 16355210
Alzheimer Dis Assoc Disord. 2018 Jan-Mar;32(1):10-17
pubmed: 29240561
Cytometry A. 2006 Jun;69(6):541-51
pubmed: 16604519
Alzheimers Dement. 2010 May;6(3):221-9
pubmed: 20451870
Curr Opin Hematol. 2011 May;18(3):166-70
pubmed: 21423014
J Clin Med. 2019 May 10;8(5):
pubmed: 31083442
Alzheimer Dis Assoc Disord. 2009 Jan-Mar;23(1):1-10
pubmed: 18703981
J Alzheimers Dis. 2018;61(2):741-752
pubmed: 29226875
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
Cell Mol Life Sci. 2013 May;70(10):1753-61
pubmed: 23475070
Neurology. 2019 Mar 12;92(11):e1256-e1267
pubmed: 30760633
Blood. 2009 Feb 26;113(9):2104-7
pubmed: 19141867