Abstract Details

Title Increased monocyte/macrophage-driven pro-inflammatory mediators associated with cerebral amyloid angiopathy

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) Aging and Dementia Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 058

Objective The objective of this study was to characterize the inflammatory milieu of the brain using mouse model of Cerebral amyloid angiopathy.

Background

Cerebral amyloid angiopathy (CAA) is a small vessel disease that causes intracerebral hemorrhage in the elderly. The clinical manifestation of CAA is the deposition of amyloid-beta peptides within the basement membrane of the cortical and leptomeningeal blood vessels, leading to cerebral microbleeds (CMBs) and cognitive impairment. However, studies investigating the effect of CAA on the aged brain inflammatory milieu are limited.

Design/Methods Tg-SwDI mice on a C57BL/6 background (13 months, symptomatic CAA mice) were used as the mouse model for CAA; age-matched wild-type (WT) mice were used as controls. Brain samples were collected after cardiac perfusion and further fractionated. Using 23-plex cytokine multiplex on brain lysates (0.1g/ml), tissue cytokines were profiled.

Results As compared to controls, symptomatic CAA mice had significantly higher levels of cytokines/chemokines; tumor necrosis factor-α (TNF-α; 54.38 vs. 17.03 pg/ml, , p=0.00207), IL-12 (70.81 vs. 53.95 pg/ml, p= 0.014), macrophage inflammatory protein-1α (MIP-1α, 113.92 vs. 16.81 pg/ml, p=0.00), MIP-1β (86.15 vs. 53.43 pg/ml, p= 0.03) and monocyte chemoattractant protein (MCP-1, 109.46 vs. 118.53 pg/ml, p= 0.00033).

Conclusions This study highlights a monocyte/macrophage driven pro-inflammatory milieu in the brains of mice with CAA pathology. Recent studies using in vivo two-photon imaging have demonstrated recruitment of monocytes/macrophages within the induced 100-µm sized microhemorrhage, further suggestive of their unique role in CAA. Pro-inflammatory cytokines such as TNF-a, IL-12, MIP-1α, MIP-1β and MCP-1 can be potential therapeutic targets for CAA as indicated by our study.

Authors/Disclosures
Carson Finger PRESENTER	Carson Finger has nothing to disclose.
Juneyoung Lee, PhD	Juneyoung Lee, PhD has nothing to disclose.
Bharti Manwani, MD (University of Texas Health Science Center Houston, McGovern Medical School)	Dr. Manwani has nothing to disclose.

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Abstract Details