title: Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases.
abstract: We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), hereditary multi-infarct dementia of Swedish type (Swedish hMID), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe. The overall sclerotic index values in frontal lobe were in the order CADASIL ≥ HERNS > PADMAL > Swedish hMID > sporadic SVD, and in basal ganglia CADASIL > HERNS > Swedish hMID > PADMAL> sporadic SVD. The subcortical white matter was almost always more affected than any gray matter. We observed glucose transporter-1 (GLUT-1) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL4) immunostaining was increased in PADMAL cases in all regions and tissue types. Overall, GLUT-1 : COL4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe. Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL.
authors: Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors: Lucinda J L
authors: LJ
authors: Craggs
authors: Christian
authors: C
authors: Hagel
authors: Gregor
authors: G
authors: Kuhlenbaeumer
authors: Anne
authors: A
authors: Borjesson-Hanson
authors: Oluf
authors: O
authors: Andersen
authors: Matti
authors: M
authors: Viitanen
authors: Hannu
authors: H
authors: Kalimo
authors: Catriona A
authors: CA
authors: McLean
authors: Janet Y
authors: JY
authors: Slade
authors: Roslyn A
authors: RA
authors: Hall
authors: Arthur E
authors: AE
authors: Oakley
authors: Yumi
authors: Y
authors: Yamamoto
authors: Vincent
authors: V
authors: Deramecourt
authors: Rajesh N
authors: RN
authors: Kalaria
mesh_terms: D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001808:Blood Vessels / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D046589:CADASIL / Q000473:pathology* / Q000503:physiopathology; D059345:Cerebral Small Vessel Diseases / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011180:Postmortem Changes; D012720:Severity of Illness Index
chemical_list: D000199:Actins
keywords: CADASIL; HERNS; PADMAL; hereditary multi-infarct dementia; sclerotic index; small vessel disease
references: Neurology. 2012 Apr 3;78(14):1043-50
references: 22377814
references: J Neurol Sci. 2004 Nov 15;226(1-2):75-80
references: 15537525
references: Brain Pathol. 2004 Oct;14(4):358-64
references: 15605982
references: Clin Exp Ophthalmol. 2005 Apr;33(2):181-3
references: 15807828
references: Neuropathol Appl Neurobiol. 2011 Feb;37(1):94-113
references: 21062344
references: Stroke. 2006 Sep;37(9):2242-7
references: 16873707
references: Acta Neuropathol. 1968 Dec 18;12(1):1-15
references: 5708546
references: Nature. 1996 Oct 24;383(6602):707-10
references: 8878478
references: Stroke. 1997 Nov;28(11):2222-9
references: 9368569
references: Acta Neuropathol. 2004 Sep;108(3):231-40
references: 15221337
references: Brain Pathol. 2002 Jul;12(3):371-84
references: 12146805
references: Stroke. 2009 Jun;40(6):2004-11
references: 19359623
references: Am J Hum Genet. 2001 Aug;69(2):447-53
references: 11438888
references: Stroke. 1999 Feb;30(2):378-82
references: 9933274
references: Bioessays. 2011 Jan;33(1):73-80
references: 20967782
references: Brain. 2007 Feb;130(Pt 2):357-67
references: 17235124
references: Nat Genet. 2007 Sep;39(9):1068-70
references: 17660820
references: J Neuroimaging. 2010 Apr;20(2):134-40
references: 19187480
references: Acta Neuropathol. 1977 Aug 31;39(3):247-54
references: 906807
references: Neurology. 1997 Nov;49(5):1322-30
references: 9371916
references: Acta Neuropathol. 1994;87(3):317-24
references: 8009965
references: J Neurol Sci. 2004 Nov 15;226(1-2):35-9
references: 15537516