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The Kilkenny Observer Friday 18 February 2022
kilkennyobserver.ie
Science & Wellbeing CIRCADIAN rhythms are the daily rhythms of bodily functions which are tied to our natural body clock, respond to light exposure, and govern our sleep-wake cycles. Poor sleep habits can throw circadian rhythms out of whack (ageing and stress also don’t help) and patchy sleep would mean less time for immune cells to cleanse the brain of waste products that build up throughout the day. Long before Alzheimer’s disease is diagnosed, oncetrusty proteins start to knot together in the brain in a process that may be hastened by poor sleep. Now, scientists have uncovered a possible mechanism linking disruptions in circadian rhythms and the buildup of proteins associated with Alzheimer’s disease, by studying the rhythmic operation of immune cells and finding the molecular ‘timers’ that control them. Sleep disturbances starting years before any symptoms emerge have been linked to a greater risk of developing Alzheimer’s disease, the most common form of dementia, and more severe symptoms. It’s long been thought that over time, clumps of misfolded proteins – including one called amyloid-beta – accumulate in the brain to cause Alzheimer’s disease, which is a neurological condition marked by memory loss and slow cognitive decline. Daily fluctuations in levels of amyloid-beta have been noted in the cerebrospinal fluid of healthy adults, but these oscillations appear to be disrupted with age, the largest risk factor for Alzheimer’s disease. However, making the direct connection between circadian rhythms and the activity of immune cells tasked with cleaning up amyloid proteins has eluded scientists thus far. In this new study, researchers led by biological scientist Jennifer Hurley of Rensselaer Polytechnic Institute in the US studied immune cells called macrophages, which are known to migrate into the RESEARCHERS at the University of Copenhagen have found several hundred different chemical substances in tap water stored in reusable plastic bottles. Several of these substances are potentially harmful to human health. There is a need for better regulation and manufacturing standards for manufacturers, according to the chemists behind the study. Several of these substances are potentially harmful to human health. There is a need for better regulation and manufacturing standards for manufacturers, according to the chemists behind the study. “We were taken aback by the large amount of chemical substances we found in water after 24 hours in the bottles. There were hundreds of substances in the water—including substances never before found in plastic, as well as substances that are potentially harmful to health. After a dishwasher
The growing link between poor sleep and Alzheimer’s
brain in late-stage Alzheimer’s disease. Macrophages are scavengers that gobble up waste products, faulty proteins, and defunct cells to prevent toxic damage. In lab-grown cell cultures observed under a microscope, these immune cells – derived from genetically modified mice with altered circadian clocks – went about cleaning up fluorescentlytagged amyloid-beta proteins
on a daily cycle. As levels of cell-surface proteins called ‘heparans’ went up, the clearance of amyloid-beta proteins slowed. But the immune cells promptly lost their rhythm when their circadian clock was disturbed, suggesting cell-surface heparans, and the protein-eating immune cells they regulate, fall under circadian control. “These data highlight that circadian regulation in im-
mune cells may play a role in the intricate relationship between the circadian clock and Alzheimer’s disease,” the team writes in their paper. Past research has found that just one night of bad sleep causes an increase in amyloid-beta proteins, and a week of sleepless nights leads to a build-up of another protein called tau, too. Chronic sleep problems could therefore spell trouble. Whether circadian clock
disruptions are a causative factor or physiological consequence of Alzheimer’s disease is still unclear, though. Keep in mind this study, which aimed to dissect possible mechanisms linking circadian clock disruptions and Alzheimer’s disease proteins, used immune cells sampled from the bone marrow of genetically modified mice as a proxy for what happens in humans. “With regard to the nature
of the circadian disruption that occurs in AD, there is much still to be understood,” behavioural neuroscientist Andrew Coogan of the University of Ireland and colleagues wrote in a 2013 review, which still rings true. It’s worth remembering, too, that amyloid proteins are not the whole story in Alzheimer’s disease. Tangles of tau proteins are the other prime suspects which have come into focus in the wake of disappointing clinical trials and mounting evidence against amyloid-beta (A ) as the main culprit of disease. “Though targeting A as a therapeutic strategy has met limited success, A accumulation is still regarded as a crucial step in AD pathogenesis,” Hurley and colleagues write. However, other recent research suggests amyloid proteins are actually latecomers to the disease rather than an early trigger, and poor sleep isn’t the only risk factor for Alzheimer’s disease. That said, pinpointing a possible mechanism that goes some way to explaining how disruptions in circadian rhythms may perturb the clearance of amyloid proteins in the brain is a good step. In a roundabout way, this work supports other lines of research looking at so-called chronotherapies, which are interventions that aim to improve people’s sleep cycles. Understanding the circadian timing of immune cells may also have implications for other disorders that like Alzheimer’s disease are linked to inflammation, including depression. “Understanding how our circadian rhythms can regulate cell-surface heparan levels to control the build-up of amyloid-beta may lead to the development of chronotherapeutics that alleviate the symptoms of Alzheimer’s disease as well as other inflammatory diseases,” Hurley says. * The study was published in PLOS Genetics.
ronmental sciences. Christensen and fellow researcher Selina Tisler detected
more than 400 different substances from the bottle plastic and over 3,500 substances derived from dishwasher soap. A large portion of these are unknown substances that the researchers have yet to identify. But even among the identified chemicals, the toxicity of at least 70% remains unknown. Photo-initiators are among the toxic substances in the water which worry the researchers. These are known to have potentially harmful effects on health in organisms, such as being endocrine disruptors and carcinogens. Furthermore, the researchers found a variety of plastic softeners, antioxidants, and release agents used in the manufacture of the plastic, as well as Diethyltoluamide (DEET), commonly known as the active substance in mosquito spray. In their experiments, the researchers mimicked the ways
in which many people typically use plastic drink bottles. People often drink water that has been kept in bottles for several hours. The researchers left ordinary tap water in both new and used drinking bottles for 24 hours, both before and after machine washing, as well as after the bottles had been in the dishwasher and rinsed thoroughly in tap water. The researchers suspect that bottle manufacturers only add a small proportion of the substances found intentionally. The majority have inadvertently occurred either during the production process or during use, where substances may have been converted from other substances. This includes the presence of the mosquito repellent DEET, where the researchers hypothesise that as one of the plastic softeners degrades, it converts into DEET.
Plastic bottles release hundreds of chemicals substances in water
cycle, there were several thousand,” says Jan H. Christensen, professor of environmental
analytical chemistry at the University of Copenhagen’s department of plant and envi-
