within each trial, as symptoms were too far progressed by the time of application to be useful. further development is still required for application to those who are presymptomatic to assess their effectiveness early into disease progression. anti-aggregation agents such as apomorphine, or carbenoxolone. the latter has commonly been used as a treatment for peptic ulcers, but also displays neuroprotective properties, shown to improve cognitive functions such as verbal fluency and memory consolidation. by binding with high affinity to aβ42 fragments, primarily via hydrogen bonding, carbenoxolone captures the peptides before they can aggregate together, rendering them inert, as well as destabilizes those aggregates already formed, helping to clear them. this is a common mechanism of action of anti-aggregation agents at large. studies comparing synthetic to recombinant aβ42 in assays measuring rate of fibrillation, fibril homogeneity, and cellular toxicity showed that recombinant aβ42 had a faster fibrillation rate and greater toxicity than synthetic amyloid beta 1-42 peptide. modulating cholesterol homeostasis has yielded results that show that chronic use of cholesterol-lowering drugs, such as the statins, is associated with a lower incidence of ad. in app genetically modified mice, cholesterol-lowering drugs have been shown to reduce overall pathology. while the mechanism is poorly understood it appears that cholesterol-lowering drugs have a direct effect on app processing. memantine is an alzheimer's disease drug which has received widespread approval. it is a non-competitive n-methyl-d-aspartate (nmda) channel blocker. by binding to the nmda receptor with a higher affinity than mg2+ ions, memantine is able to inhibit the prolonged influx of ca2+ ions, particularly from extrasynaptic receptors, which forms the basis of neuronal excitotoxicity. it is an option for the management of those with moderate to severe alzheimer's disease (modest effect). the study showed that 20 mg/day improved cognition, functional ability and behavioural symptoms. measuring amyloid beta micrograph showing amyloid beta (brown) in amyloid plaques of the cerebral cortex (upper left of image) and cerebral blood vessels (right of image) with immunostaining imaging compounds, notably pittsburgh compound b, (6-oh-bta-1, a thioflavin), can selectively bind to amyloid beta in vitro and in vivo. this technique, combined with pet imaging, is used to image areas of plaque deposits in those with alzheimer's. post mortem or in tissue biopsies amyloid beta can be measured semiquantitatively with immunostaining, which also allows one to determine location. amyloid beta may be primarily vascular, as in cerebral amyloid angiopathy, or in amyloid plaques in white matter. one sensitive method is elisa which is an immunosorbent assay which utilizes a pair of antibodies that recognize amyloid beta. atomic force microscopy, which can visualize nanoscale molecular surfaces, can be used to determine the aggregation state of amyloid beta in vitro. vibrational microspectroscopy is a label-free method that measures the vibration of molecules in tissue samples. amyloid proteins like aβ can be detected with this technique because of their high content of β-sheet structures. recently, the formation of aβ fibrils was resolved in different plaque-types in alzheimer's disease, indicating that plaques transit different stages in their development. dual polarisation interferometry is an optical technique which can measure early stages of aggregation by measuring the molecular size and densities as the fibrils elongate. these aggregate processes can also be studied on lipid bilayer constructs.