One way to image the molecular pathology in Alzheimer’s disease (AD) is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early stage biomarkers that instigate memory loss comprise of Aβ oligomers (AβOs). Here we report a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for AβOs. We attach oligomer-specific antibodies onto magnetic nanostructures and show the complex is stable and it binds to AβOs on cells and brain tissues to give a MRI signal. When intranasally administered to an AD mouse model, the probe readily reached hippocampal AβOs. In isolated samples of human brain tissue, we observed an MRI signal that distinguished AD from controls. Such nanostructures that target neurotoxic AβOs are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage AD diagnosis and disease management.
Introduction A decline in sleep quality and reduction in slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate variability in post-menopausal women. Methods Twenty-four healthy postmenopausal women between 40–75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress(LHCM) a week apart. Sleep was recorded using polysomnography during an 8-hour sleep opportunity. Core and peripheral temperatures were recorded using Equivital and ibutton respectively. Results In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 minutes (2.1%), p = 0.04) and in slow oscillatory activity (0.5-1Hz) in the first NREM/REM cycle (p=0.04). In addition, the HHCM induced a greater reduction in core body temperature (p=0.002), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 4.66±0.17°C). Average heart rate was 2.7 beats/minute lower across the night on the HHCM compared to the LHCM (p=0.001). Conclusion The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep and cardiovascular function in postmenopausal women. Support Technogel
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