title: Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.
abstract: The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets.
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: James L
authors.initials: JL
authors.lastname: Searcy
authors.affiliation: SynthSys - Synthetic & Systems Biology, University of Edinburgh, Edinburgh, United Kingdom ; Institute of Structural and Molecular Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Bihan
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Natalia
authors.initials: N
authors.lastname: Salvadores
authors.affiliation: Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, United Kingdom ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: McCulloch
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Horsburgh
mesh_terms: D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002853:Chromatography, Liquid; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D063990:Gene Ontology; D000074289:High-Temperature Requirement A Serine Peptidase 1; D015151:Immunoblotting; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D020543:Proteome; D016601:RNA-Binding Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases