CANINE LEPTOMENINGEAL ORGAN-CULTURE - A NEW EXPERIMENTAL-MODEL FOR CEREBROVASCULAR BETA-AMYLOIDOSIS

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Al zheimer's disease and a common cause of cerebral hemorrhage in the eld erly. The pathogenetic mechanisms leading to the deposition of Alzheim er amyloid beta-protein (A beta) in cortical and leptomeningeal vessel walls are unknown. There are no experimental models which reproduce t he pathological changes of CAA. In this study, leptomeninges from youn g and old dogs with pre-existing CAA were cultured in cell culture med ium or cerebrospinal fluid and their viability, histological appearanc e and metabolic activity were analyzed during the culture. In addition , living leptomeninges of old and young dogs were incubated with fluor escein-conjugated A beta and the uptake of A beta was studied by fluor escence microscopy. Leptomeninges from young and old dogs were viable up to 8 weeks in culture. They contain many small- and medium-sized ar terioles, the main vessel type affected by CAA. Histology and immunohi stochemistry showed excellent preservation of the vessel wall microarc hitecture up to 4 weeks in culture. The cultures were metabolically ac tive as shown by the de novo production of beta-amyloid precursor prot ein. Exogenously added A beta was focally deposited in the vessel wall s of old, but not young dogs. In conclusion, the organ culture of cani ne leptomeninges is easy to perform and appears suitable to investigat e the pathogenesis and the progression of CAA.