Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina.
Aged
Aged, 80 and over
Alzheimer Disease
/ pathology
Amyloid beta-Peptides
/ metabolism
Amyloid beta-Protein Precursor
/ metabolism
Amyloidosis
/ complications
Blood-Brain Barrier
/ pathology
Brain
/ pathology
Cerebral Amyloid Angiopathy
/ pathology
Cognition
/ physiology
Female
Humans
Male
Pericytes
/ pathology
Retina
/ pathology
Alzheimer’s disease
Cerebral amyloid angiopathy
Neurodegeneration
Pericytes
Retinopathy
Vascular damage
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
31
10
2019
accepted:
02
02
2020
revised:
17
01
2020
pubmed:
12
2
2020
medline:
9
6
2021
entrez:
12
2
2020
Statut:
ppublish
Résumé
Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ
Identifiants
pubmed: 32043162
doi: 10.1007/s00401-020-02134-w
pii: 10.1007/s00401-020-02134-w
pmc: PMC7181564
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
813-836Subventions
Organisme : NIA NIH HHS
ID : R01 AG055865
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056478
Pays : United States
Références
Acta Neuropathol. 2016 Dec;132(6):767-787
pubmed: 27645291
Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14354-9
pubmed: 23918361
JAMA Ophthalmol. 2018 Nov 1;136(11):1242-1248
pubmed: 30352114
Ann Neurol. 2011 Feb;69(2):320-7
pubmed: 21387377
Alzheimers Dement (Amst). 2016 Oct 01;4:169-178
pubmed: 27830174
Front Physiol. 2018 Dec 06;9:1721
pubmed: 30574092
J Cereb Blood Flow Metab. 2016 Jan;36(1):216-27
pubmed: 25757756
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Brain Pathol. 2014 Jul;24(4):371-86
pubmed: 24946075
Acta Neuropathol. 2009 Jul;118(1):103-13
pubmed: 19319544
Ann N Y Acad Sci. 1999;893:314-20
pubmed: 10672257
Invest Ophthalmol Vis Sci. 2007 May;48(5):2285-9
pubmed: 17460292
Neuron. 2005 Jul 21;47(2):191-199
pubmed: 16039562
J Alzheimers Dis. 2010;22(1):1-16
pubmed: 20847434
Neuroreport. 2011 Aug 24;22(12):623-7
pubmed: 21734608
J Neuropathol Exp Neurol. 2004 Jul;63(7):735-41
pubmed: 15290898
J Biol Chem. 1995 Mar 31;270(13):7013-6
pubmed: 7706234
Neurology. 1991 Apr;41(4):479-86
pubmed: 2011243
Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3231-8
pubmed: 27333181
Brain. 2014 May;137(Pt 5):1533-49
pubmed: 24625695
Transl Psychiatry. 2013 Feb 26;3:e233
pubmed: 23443359
J Clin Invest. 2000 Nov;106(9):1159-66
pubmed: 11067868
J Pharm Sci. 2011 Sep;100(9):3904-11
pubmed: 21638281
Neurobiol Aging. 1996 May-Jun;17(3):385-95
pubmed: 8725900
Ann Neurol. 1989 Aug;26(2):226-31
pubmed: 2774510
Ann Neurol. 2016 Jan;79(1):90-109
pubmed: 26505992
J Chem Neuroanat. 2018 Oct;92:48-60
pubmed: 29885791
JAMA. 2017 Oct 10;318(14):1314
pubmed: 29049570
IEEE Rev Biomed Eng. 2010;3:169-208
pubmed: 22275207
Invest Ophthalmol Vis Sci. 1993 May;34(6):2097-104
pubmed: 8491560
Neurology. 2018 Mar 27;90(13):e1158-e1166
pubmed: 29490915
Nature. 2006 Oct 12;443(7112):700-4
pubmed: 17036005
Neuron. 2010 Nov 4;68(3):409-27
pubmed: 21040844
J Cereb Blood Flow Metab. 2012 Oct;32(10):1841-52
pubmed: 22850407
J Clin Invest. 2000 Dec;106(12):1489-99
pubmed: 11120756
Development. 1999 Jun;126(14):3047-55
pubmed: 10375497
Neurology. 2015 Dec 1;85(22):1930-6
pubmed: 26537052
PLoS One. 2017 Apr 25;12(4):e0176225
pubmed: 28441414
Nat Commun. 2019 Sep 17;10(1):4227
pubmed: 31530809
J Neuropathol Exp Neurol. 1998 Apr;57(4):353-9
pubmed: 9600229
Ann Neurol. 2011 Dec;70(6):871-80
pubmed: 22190361
Nat Rev Neurosci. 2011 Nov 03;12(12):723-38
pubmed: 22048062
Front Neurol. 2017 Dec 19;8:701
pubmed: 29312125
Nat Commun. 2013;4:2932
pubmed: 24336108
Arch Biochem Biophys. 1993 Feb 15;301(1):41-52
pubmed: 8442665
J Cereb Blood Flow Metab. 2013 Oct;33(10):1500-13
pubmed: 23921899
Dement Geriatr Cogn Disord. 2011;31(2):126-31
pubmed: 21282950
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7622-E7631
pubmed: 28827364
Invest Ophthalmol Vis Sci. 2013 Dec 19;54(13):8237-50
pubmed: 24150762
J Clin Invest. 2017 Sep 1;127(9):3210-3219
pubmed: 28862640
ACS Chem Neurosci. 2018 Apr 18;9(4):790-799
pubmed: 29232098
Arch Ophthalmol. 2000 Oct;118(10):1364-9
pubmed: 11030818
Acta Neuropathol. 2006 Oct;112(4):389-404
pubmed: 16906426
JCI Insight. 2017 Aug 17;2(16):
pubmed: 28814675
Alzheimer Dis Assoc Disord. 2010 Apr-Jun;24(2):138-42
pubmed: 20505431
Curr Protoc Mouse Biol. 2015 Sep 01;5(3):247-270
pubmed: 26331759
J Alzheimers Dis. 2011;24(1):25-34
pubmed: 21157031
Cell Mol Neurobiol. 2016 Mar;36(2):181-94
pubmed: 26993512
Mol Neurodegener. 2010 Aug 25;5:32
pubmed: 20738866
Curr Alzheimer Res. 2015;12(1):32-46
pubmed: 25523424
Neurodegener Dis. 2012;10(1-4):285-93
pubmed: 22343730
Curr Alzheimer Res. 2007 Apr;4(2):191-7
pubmed: 17430246
ASN Neuro. 2014 Dec 12;6(6):
pubmed: 25504540
Brain. 2015 Aug;138(Pt 8):2399-422
pubmed: 26049087
J Neuropathol Exp Neurol. 2003 Dec;62(12):1287-301
pubmed: 14692704
Ophthalmic Res. 2018;59(4):182-192
pubmed: 29621759
J Neurosci Res. 2000 Jun 15;60(6):804-10
pubmed: 10861793
Brain. 2015 Dec;138(Pt 12):3716-33
pubmed: 26598495
Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3447-3455
pubmed: 31408108
PLoS One. 2015 Aug 07;10(8):e0134750
pubmed: 26252902
Eur J Ophthalmol. 2011;21 Suppl 6:S3-9
pubmed: 23264323
Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1491-1500
pubmed: 30973577
Mol Neurodegener. 2018 Oct 19;13(1):57
pubmed: 30340601
Acta Neuropathol Commun. 2018 Dec 28;6(1):147
pubmed: 30593285
Alzheimers Dement. 2012 Jan;8(1):1-13
pubmed: 22265587
Front Aging Neurosci. 2018 Jun 22;10:188
pubmed: 29988470
Neurology. 1993 Nov;43(11):2412-4
pubmed: 8232972
Neuron. 1994 Jul;13(1):45-53
pubmed: 8043280
CNS Neurol Disord Drug Targets. 2009 Mar;8(1):16-30
pubmed: 19275634
Stroke. 2007 Jul;38(7):2041-7
pubmed: 17525385
Neurology. 2002 Jun 25;58(12):1791-800
pubmed: 12084879
Neuroimage. 2011 Jan;54 Suppl 1:S204-17
pubmed: 20550967