Abstract Details

Title Sex Differences in Cerebral Amyloid Angiopathy: The Role of Monocytes/ Macrophages

Topic Behavioral and Cognitive Neurology

Presentation(s) S2 - Behavioral Neurology (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background Cerebral amyloid angiopathy is a known cause of cognitive impairment and intracerebral hemorrhage in the elderly. Cerebral microbleeds (CMBs) detected on MRI are the diagnostic hallmarks of this disease. Recent studies have shown increased CMBs and worst cognition in female CAA mice as compared to males. The underlying mechanisms for this sexual dichotomy are unclear. We hypothesized that increased inflammatory response in females contributes to neuronal damage and cognitive decline in CAA.

Objective

The objective of this study was to discern sex differences in inflammatory pathways in Cerebral Amyloid Angiopathy (CAA)

Design/Methods C57BL6 Tg-SwDI male and female mice (12 months) were used as a mouse model for CAA. Peripheral blood and brain tissues were collected and single cell suspensions were acquired for immunophenotyping using flow cytometry. We used CD45, CD11b, Ly6C and CD3 antibodies to gate for monocytes/macrophages (CD45highCD11b+Ly6C+) and T cells (CD45highCD11b- CD3+) respectively. Data was analyzed using two sample t-test on GraphPad PRISM.

Results Our results demonstrated that in the peripheral blood, Tg-SwDI female mice had significantly increased frequency of monocytes/macrophages as compared to males (Females, 64±8.1%, n=10 vs. males, 33.9±6.9%, n=8, p=0.01). Similar to peripheral blood, there were significantly increased monocytes/macrophages in the female brain (Females, 36.5±6.3%, n=10, vs. males, 20.9±2.7%, n=8, p= 0.04). No significant differences were seen in T cells in the blood (Females, 27±4.3% vs. males, 26.9±3.3%, p= 0.9) or brain (57.2±6.8% vs. 65.3±5.4%, p= 0.3).

Conclusions Recent studies suggest that vascular Aβ accumulation in CAA causes an innate inflammatory response, leading to further cognitive decline and CMB formation. Our results highlight a monocyte/macrophage driven pro-inflammatory milieu in female CAA mice which may contribute to worse outcomes. Regulation of monocytes/ macrophages and their cytokine-mediated inflammatory pathways may be a potential sex specific therapeutic target in CAA.

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.