Canine leptomeningeal organ culture: a new experimental model for cerebrovascular beta-amyloidosis.

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Alzheimer's disease and a common cause of cerebral hemorrhage in the elderly. The pathogenetic mechanisms leading to the deposition of Alzheimer amyloid beta-protein (A beta) in cortical and leptomeningeal vessel walls are unknown. There are no experimental models which reproduce the pathological changes of CAA. In this study, leptomeninges from young and old dogs with pre-existing CAA were cultured in cell culture medium or cerebrospinal fluid and their viability, histological appearance and metabolic activity were analyzed during the culture. In addition, living leptomeninges of old and young dogs were incubated with fluorescein-conjugated A beta and the uptake of A beta was studied by fluorescence microscopy. Leptomeninges from young and old dogs were viable up to 8 weeks in culture. They contain many small- and medium-sized arterioles, the main vessel type affected by CAA. Histology and immunohistochemistry showed excellent preservation of the vessel wall microarchitecture up to 4 weeks in culture. The cultures were metabolically active as shown by the de novo production of beta-amyloid precursor protein. Exogenously added A beta was focally deposited in the vessel walls of old, but not young dogs. In conclusion, the organ culture of canine leptomeninges is easy to perform and appears suitable to investigate the pathogenesis and the progression of CAA.