LAUSR

Accumulation of β amyloid in leptomeningeal vessels and cortical arterioles is the hallmark of cerebral amyloid angiopathy, this causes vessel stiffening, and vessel wall rupture. Alzheimer’s disease amyloid plaques are composed of β-amyloid 42, whilst CAA results from accumulation of the β-amyloid 40, although β-amyloid 40 may migrate to the vasculature from parenchymal plaques. Recent work has shown that inefficient clearance of amyloid, rather than excess production is the primary contributor to β amyloid accumulation. Early work using a variety of approaches to increase clearance of β-amyloid, suggested a possible excess of micro-haemorrhages in animal models. A recent study from this group showed that chronic administration of high dose Ponezumab (a monoclonal antibody targeting β-amyloid) in an older group of transgenic mice did not increase micro-haemorrhage. This study tested the efficiency of β-amyloid clearance from the vasculature, and the consequences of β-amyloid clearance on vascular reactivity. Transgenic mice between 6 and 22 months were used. These were from a variety of strains—APP knock-in, compound knock-in APP-PS1 and APP PSdE9 compound knockin animals. Multi-photon imaging used methoxy x-034 to label amyloid and pre-imaging rhodamine injection to track blood vessels. Animals were imaged on a monthly basis. The brains were then removed and lysed, using centrifugation, the vascular tissue was separated from cortical regions and myelin. ELISA was used to measure β-amyloid Introduction