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Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.

Searcy JL, Le Bihan T, Salvadores N, McCulloch J, Horsburgh K - PLoS ONE (2014)

Bottom Line: The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis.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).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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.

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.

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Related in: MedlinePlus

Increases in APOE levels are specific to 9 mos Tg-SwDI mice.Tissue sections representative of independent 3 and 9 month-old WT (A&B) and 3 and 9 month-old Tg-SwDI (C&D) animals were triple-labelled with APOE (red), 6E10 (green) and β-dystroglycan (magenta) and analysed with a laser scanning confocal microscope within the thalamus (400×). Immunohistochemical analysis of the four different cohorts show APOE and Aβ present only in the (D) 9 month Tg-SwDI animals. APOE co-localized (shown in white) with both (E) 6E10-labelled Aβ and (F) β-dystroglycan-labelled cerebral vessels. (G) Aβ is closely associated with cerebral vessels.
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pone-0089970-g007: Increases in APOE levels are specific to 9 mos Tg-SwDI mice.Tissue sections representative of independent 3 and 9 month-old WT (A&B) and 3 and 9 month-old Tg-SwDI (C&D) animals were triple-labelled with APOE (red), 6E10 (green) and β-dystroglycan (magenta) and analysed with a laser scanning confocal microscope within the thalamus (400×). Immunohistochemical analysis of the four different cohorts show APOE and Aβ present only in the (D) 9 month Tg-SwDI animals. APOE co-localized (shown in white) with both (E) 6E10-labelled Aβ and (F) β-dystroglycan-labelled cerebral vessels. (G) Aβ is closely associated with cerebral vessels.

Mentions: Tissue from independent cohorts of 3 month-old WT, 9 month-old WT, 3 month-old Tg-SwDI and 9 month-old Tg-SwDI mice were immunolabelled with antibodies to β-dystroglycan, Aβ and APOE. APOE immunolabelling was mostly observed in 9 month-old Tg-SwDI animals (Figure 7A–D). APOE co-localized to both accumulated Aβ and cerebral vessels, particularly those vessels proximate to Aβ deposits within the thalamus.


Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.

Searcy JL, Le Bihan T, Salvadores N, McCulloch J, Horsburgh K - PLoS ONE (2014)

Increases in APOE levels are specific to 9 mos Tg-SwDI mice.Tissue sections representative of independent 3 and 9 month-old WT (A&B) and 3 and 9 month-old Tg-SwDI (C&D) animals were triple-labelled with APOE (red), 6E10 (green) and β-dystroglycan (magenta) and analysed with a laser scanning confocal microscope within the thalamus (400×). Immunohistochemical analysis of the four different cohorts show APOE and Aβ present only in the (D) 9 month Tg-SwDI animals. APOE co-localized (shown in white) with both (E) 6E10-labelled Aβ and (F) β-dystroglycan-labelled cerebral vessels. (G) Aβ is closely associated with cerebral vessels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935958&req=5

pone-0089970-g007: Increases in APOE levels are specific to 9 mos Tg-SwDI mice.Tissue sections representative of independent 3 and 9 month-old WT (A&B) and 3 and 9 month-old Tg-SwDI (C&D) animals were triple-labelled with APOE (red), 6E10 (green) and β-dystroglycan (magenta) and analysed with a laser scanning confocal microscope within the thalamus (400×). Immunohistochemical analysis of the four different cohorts show APOE and Aβ present only in the (D) 9 month Tg-SwDI animals. APOE co-localized (shown in white) with both (E) 6E10-labelled Aβ and (F) β-dystroglycan-labelled cerebral vessels. (G) Aβ is closely associated with cerebral vessels.
Mentions: Tissue from independent cohorts of 3 month-old WT, 9 month-old WT, 3 month-old Tg-SwDI and 9 month-old Tg-SwDI mice were immunolabelled with antibodies to β-dystroglycan, Aβ and APOE. APOE immunolabelling was mostly observed in 9 month-old Tg-SwDI animals (Figure 7A–D). APOE co-localized to both accumulated Aβ and cerebral vessels, particularly those vessels proximate to Aβ deposits within the thalamus.

Bottom Line: The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis.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).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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus