Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

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In addition to classical run-in and steady-state wear phases, metal-on-metal (MOM) hip bearings have encountered "runaway wear" (RAW) trends in simulator studies. This puzzling behavior has resulted in 2- to 19-fold wear increases compared with other apparently "identical" bearings. MOM bearings have shown five identifiable RAW wear patterns in joint simulators; therefore, additional descriptive terms were used here to indicate various observed patterns, for example, "breakaway wear" (BAW), which was defined as a higher wear trend that recovers to steady-state wear. As these trends commonly occur for MOM, this raises the question of what can be considered "normal" behavior or "abnormal"? In an effort to identify possible causes for this behavior, the current study investigated six Co-Cr bearings, which closely matched with respect to geometrical tolerances. Despite close control of design and test variables, BAW occurred in 30% of the MOM bearings, producing a threefold wear increase above otherwise identical MOM bearings within the same group. The majority of the BAW (85%) occurred on the cup side and was validated by growth of wear scars and concentrations of metal ions. One bearing that showed continuing BAW at 5 Mc revealed a cup that was 50% smoother than other cups whereas its mating head was 50% rougher, thus signifying that highly polished areas were sites of the highest MOM wear. The two BAW bearings with high wear showed the greatest conformity at 5 Mc, in apparent contradistinction to classical lubrication theory.

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