Quantitative Vascular Pathology and Phenotyping Familial and Sporadic Cerebral Small Vessel Diseases
Lucinda J. L. Craggs,Christian Hagel,Gregor Kuhlenbaeumer,Anne Börjesson-Hanson,Oluf Andersen,Matti Viitanen,Hannu Kalimo,Catriona McLean,Janet Y. Slade,Roslyn Hall,Arthur E. Oakley,Yumi Yamamoto,Vincent Deramecourt,Rajesh N. Kalaria +13 more
TLDR
Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe, shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end‐stage pathologies.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.read more
Citations
More filters
Journal ArticleDOI
Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease
TL;DR: New observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology.
Journal ArticleDOI
Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline
Leif Østergaard,Leif Østergaard,Thorbjørn S Engedal,Fiona Moreton,M. Hansen,Joanna M. Wardlaw,Turgay Dalkara,Hugh S. Markus,Keith W. Muir +8 more
TL;DR: Whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD and aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline are examined.
Journal ArticleDOI
White matter changes in dementia: role of impaired drainage of interstitial fluid.
TL;DR: Facilitating perivascular lymphatic drainage from the aging brain may play a significant role in the prevention of CAA, WMH and Alzheimer's disease and may enhance the efficacy of immunotherapy for Alzheimer's Disease.
Journal ArticleDOI
White matter degeneration in vascular and other ageing-related dementias
TL;DR: It is demonstrated that WM degeneration encompasses multiple substrates and therefore more than one pharmacological approach is necessary to preserve axonal function and prevent cognitive impairment.
Journal ArticleDOI
Hypertension and the Brain: A Risk Factor for More Than Heart Disease.
TL;DR: There is an urgent need to understand the mechanisms underlying hypertension-induced cerebrovascular complications in order to identify effective therapeutic targets to prevent and most importantly also reverse cognitive decline mediated through hypertension.
References
More filters
Journal ArticleDOI
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Anne Joutel,Christophe Corpechot,Anne Ducros,Katayoun Vahedi,Hugues Chabriat,Philippe Mouton,Sonia Alamowitch,Valérie Domenga,Michaelle Cécillion,Emmanuelle Maréchal,Jacqueline Maciazek,Céline Vayssière,Corinne Cruaud,E. A. Cabanis,Marie Madeleine Ruchoux,Jean Weissenbach,Jean Francois Bach,Marie-Germaine Bousser,Elisabeth Tournier-Lasserve +18 more
TL;DR: The characterization of the human Notch3 gene, which was previously mapped to the CADASIL critical region, is reported, indicating that Notch 3 could be the defective protein in CADASil patients.
Journal ArticleDOI
The arterial lesions underlying lacunes.
TL;DR: There was a total occlusion of the artery supplying the territory of the infarct in 45 of 50 consecutive lacunes, and segmental arterial disorganization has been discussed in some detail.
Journal ArticleDOI
C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy
Anna Richards,Arn M. J. M. van den Maagdenberg,Joanna C. Jen,David J. Kavanagh,Paula Bertram,Dirk Spitzer,M. Kathryn Liszewski,Maria Louise Barilla-Labarca,Gisela M. Terwindt,Yumi Kasai,Michael D. McLellan,Mark Gilbert Grand,Kaate R J Vanmolkot,Boukje de Vries,Jijun Wan,Michael J. Kane,Hafsa Mamsa,Ruth Schäfer,Anine H. Stam,Joost Haan,Paulus T. V. M. de Jong,Paulus T. V. M. de Jong,Caroline W. Storimans,Mary J. van Schooneveld,J. A. Oosterhuis,Andreas Gschwendter,Martin Dichgans,Katya E. Kotschet,Suzanne Hodgkinson,Todd A. Hardy,Martin B. Delatycki,Rula A. Hajj-Ali,Parul H. Kothari,Stanley F. Nelson,Rune R. Frants,Robert W. Baloh,Michel D. Ferrari,John P. Atkinson +37 more
TL;DR: Heterozygous C-terminal frameshift mutations in TREX1 retain exonuclease activity but lose normal perinuclear localization, which has implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.
Journal ArticleDOI
Towards defining the neuropathological substrates of vascular dementia.
TL;DR: The neuropathological substrates of VaD also need to be better defined to impact on preventative and treatment strategies and are critical for selective recruitment to clinical trials.
Journal ArticleDOI
CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia
TL;DR: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to cognitive decline and dementia, and it is as yet unclear which disturbance in the Notch signaling pathway leads to the characteristic vascular pathology of CADASIL.