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Systems proteomic analysis reveals that clusterin and tissue inhibitor of metalloproteinases 3 increase in leptomeningeal arteries affected by cerebral amyloid angiopathy.
Manousopoulou, A; Gatherer, M; Smith, C; Nicoll, J A R; Woelk, C H; Johnson, M; Kalaria, R; Attems, J; Garbis, S D; Carare, R O.
Afiliação
  • Manousopoulou A; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Gatherer M; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Smith C; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Nicoll JAR; Pathology Department, University of Edinburgh, Edinburgh, UK.
  • Woelk CH; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Johnson M; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Kalaria R; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
  • Attems J; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
  • Garbis SD; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
  • Carare RO; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Neuropathol Appl Neurobiol ; 43(6): 492-504, 2017 Oct.
Article em En | MEDLINE | ID: mdl-27543695
ABSTRACT

AIMS:

Amyloid beta (Aß) accumulation in the walls of leptomeningeal arteries as cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease. In this study, we used global quantitative proteomic analysis to examine the hypothesis that the leptomeningeal arteries derived from patients with CAA have a distinct endophenotypic profile compared to those from young and elderly controls.

METHODS:

Freshly dissected leptomeningeal arteries from the Newcastle Brain Tissue Resource and Edinburgh Sudden Death Brain Bank from seven elderly (82.9 ± 7.5 years) females with severe capillary and arterial CAA, as well as seven elderly (88.3 ± 8.6 years) and five young (45.4 ± 3.9 years) females without CAA were used in this study. Arteries from four patients with CAA, two young and two elderly controls were individually analysed using quantitative proteomics. Key proteomic findings were then validated using immunohistochemistry.

RESULTS:

Bioinformatics interpretation of the results showed a significant enrichment of the immune response/classical complement and extracellular matrix remodelling pathways (P < 0.05) in arteries affected by CAA vs. those from young and elderly controls. Clusterin (apolipoprotein J) and tissue inhibitor of metalloproteinases-3 (TIMP3), validated using immunohistochemistry, were shown to co-localize with Aß and to be up-regulated in leptomeningeal arteries from CAA patients compared to young and elderly controls.

CONCLUSIONS:

Global proteomic profiling of brain leptomeningeal arteries revealed that clusterin and TIMP3 increase in leptomeningeal arteries affected by CAA. We propose that clusterin and TIMP3 could facilitate perivascular clearance and may serve as novel candidate therapeutic targets for CAA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Peptídeos beta-Amiloides / Angiopatia Amiloide Cerebral / Inibidor Tecidual de Metaloproteinase-3 / Clusterina Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Peptídeos beta-Amiloides / Angiopatia Amiloide Cerebral / Inibidor Tecidual de Metaloproteinase-3 / Clusterina Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article