Journal of Clinical & Experimental Pathology
Open Access

Abstract

Cerebral amyloid angiopathy (CAA) is frequently observed in Alzheimerâ�?�?s disease (AD) and is marked by deposition of amyloid beta (A�?²) in leptomeningeal and cortical brain vasculature. In over 40% of AD cases, A�?² accumulates in cortical capillaries, a phenomenon referred to as capillary CAA (capCAA), which is associated with loss of tight junction proteins and a reduced function of P-glycoprotein, indicating impaired function of the blood brain barrier (BBB) and decreased transport of amyloid beta across the BBB. Increasing evidence suggests that an altered sphingolipid (SL) metabolism contributes to Alzheimer's disease. However, to date it remains unknown if alteration of the SL pathway is involved in capCAA pathogenesis. In this study we set out to investigate the alterations of the different players of the SL pathway in capCAA. Expression and localization of ceramide, sphingosine-1-phosphate (S1P) receptors (S1P1, S1P3) and the enzyme involved in ceramide production, acid sphingomyelinase (ASM), were assessed using immunohistochemistry on post-mortem tissue from the occipital cortex of non-neurological controls, AD and severe capCAA cases. Increased immunoreactivity for ceramide, S1P3, S1P1 and ASM was observed in capCAA cases compared to non-neurological controls and AD cases. Immunoreactivity for ceramide and S1P3 was primarily observed in astrocytes, whereas immunoreactivity for S1P1 and ASM was observed in microglia. In capCAA, all SL markers showed high levels of immunoreactivity around amyloidladen capillaries and correlated with the presence GFAP and HLA-DR as markers for glial activation. We find increased presence of SL pathway markers in AD cases with capCAA. The increased presence of these markers in glial cells associated amyloid-laden capillaries, suggests that the SL pathway is involved in the neuroinflammatory response in capCAA pathogenesis. Future studies are needed to address the functional role of the SL pathway in capCAA pathology.

Biography

Email: hripsimesnkhchyan@yandex.com