Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases

TY - JOUR

T1 - Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases

AU - Craggs, Lucinda J L

AU - Hagel, Christian

AU - Kuhlenbaeumer, Gregor

AU - Borjesson-Hanson, Anne

AU - Andersen, Oluf

AU - Viitanen, Matti

AU - Kalimo, Hannu

AU - McLean, Catriona A

AU - Slade, Janet Y

AU - Hall, Roslyn A

AU - Oakley, Arthur E

AU - Yamamoto, Yumi

AU - Deramecourt, Vincent

AU - Kalaria, Rajesh N

N1 - © 2013 International Society of Neuropathology.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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.

AB - 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.

KW - Actins

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Analysis of Variance

KW - Blood Vessels

KW - Brain

KW - CADASIL

KW - Cerebral Small Vessel Diseases

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Postmortem Changes

KW - Severity of Illness Index

U2 - 10.1111/bpa.12041

DO - 10.1111/bpa.12041

M3 - SCORING: Journal article

C2 - 23387519

VL - 23

SP - 547

EP - 557

JO - BRAIN PATHOL

JF - BRAIN PATHOL

SN - 1015-6305

IS - 5

ER -