Your new post is loading...
|
Scooped by
Juan Lama
|
Alzheimer’s disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms. Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance. A small number of patients who received growth hormone preparations contaminated with seeds of the amyloid-beta protein developed Alzheimer’s disease many years after treatment. Published in Nature Medicine (Jan. 29, 2024): https://doi.org/10.1038/s41591-023-02729-2
|
Scooped by
Juan Lama
|
Researchers at Baylor College of Medicine report today in the journal Neuron evidence that refutes the link between increased levels of herpes virus and Alzheimer's disease. In addition, the researchers provide a new statistical and computational framework for the analysis of large-scale sequencing data. About 50 million people worldwide are affected by Alzheimer's disease, a type of progressive dementia that results in the loss of memory, cognitive abilities and verbal skills, and the numbers are growing rapidly. Currently available medications temporarily ease the symptoms or slow the rate of decline, which maximizes the time patients can live and function independently. However, there are no treatments to halt progression of Alzheimer's disease. "Like all types of dementia, Alzheimer's disease is characterized by massive death of brain cells, the neurons. Identifying the reason why neurons begin and continue to die in the brains of Alzheimer's disease patients is an active area of research," said corresponding author Dr. Zhandong Liu, associate professor of pediatrics at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. One theory that has gained traction in the past year is that certain microbial infections, such as those caused by viruses, can trigger Alzheimer's disease. A 2018 study reported increased levels of human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) in the postmortem brain tissues of more than 1,000 patients with Alzheimer's disease when compared to the brain tissues of healthy-aging subjects or those suffering from a different neurodegenerative condition. Presence of elevated levels of genetic material of herpes viruses indicated active infections, which were linked to Alzheimer's disease. In less than a year, this study generated a flurry of excitement and led to the initiation of several studies to better understand the link between viral infections and Alzheimer's disease. Surprisingly, when co-author Dr. Hyun-Hwan Jeong, a postdoctoral fellow in Dr. Liu's group and others, reanalyzed the data sets from the 2018 study using the identical statistical methods with rigorous filtering, as well as four commonly used statistical tools, they were unable to produce the same results. The team was motivated to reanalyze the data from the previous study because they observed that while the p-values (a statistical parameter that predicts the probability of obtaining the observed results of a test, assuming that other conditions are correct) were highly significant, they were being ascribed to data in which the differences were not visually appreciable. Moreover, the p-values did not fit with simple logistic regression—a statistical analysis that predicts the outcome of the data as one of two defined states. In fact, after several types of rigorous statistical tests, they found no link between the abundance of herpes viral DNA or RNA and likelihood of Alzheimer's disease in this cohort... Published in Neuron (December 18, 2019): https://doi.org/10.1016/j.neuron.2019.11.009
|
Scooped by
Juan Lama
|
A new finding that even took the study’s authors by surprise lends support to the controversial idea that microbes play a role in Alzheimer’s disease. The research published June 21 in Neuron, found convincing signs that certain types of herpes virus may promote the complex process that leads to the disease that afflicts some 5.7 million Americans. The study points to the viruses as possible accomplices that drive disease progression but does not suggest that Alzheimer’s may begin after they are transmitted through casual contact. Joel Dudley, a geneticist and genomic scientist at the Icahn School of Medicine at Mount Sinai and senior author of the new paper, had not intended to investigate this theory when his lab began working on the newly published study in 2013. The plan he had made with colleagues was to identify possible new Alzheimer’s drug targets by looking at the molecular changes in the brain that occur during the disease. Thanks to a new NIH-led public-private partnership called the Accelerating Medicines Partnership Alzheimer's Disease (AMP-AD), the team had access to data from 876 brains—some healthy and some with early- or late-stage Alzheimer’s. They used DNA and RNA sequencing to parse out genetic differences between the groups as well as differences in how inherited genes were expressed or made into RNA. That’s when they started getting strange results. “The algorithms kept returning this pattern for viral biology,” Dudley says. The team found more viral DNA in Alzheimer’s brains compared with healthy brains—specifically, high levels of DNA from human herpesvirus 6A (HHV-6A). RNA of both HHV-6A and HHV-7 were also higher in the Alzheimer’s brains than in healthy brains, and viral RNA levels tracked with the severity of clinical symptoms. HHV-6A is a usually symptom-less virus that infects people later in life. HHV-7 infects more than 80 percent of infants, often causing a rash. Original research Published in Neuron on June 21, 2018 https://doi.org/10.1016/j.neuron.2018.05.023
|
|
Scooped by
Juan Lama
|
A recent study of more than 6 million people 65 and older found that seniors who had Covid-19 had a substantially higher risk of being diagnosed with Alzheimer's disease within a year. The study does not show that Covid-19 causes Alzheimer's, but it adds to the growing body of research drawing links between coronavirus infection and cognitive function. In the Alzheimer's disease brain, the pathology starts to build up about 20 years before the symptoms begin," said Dr. David Holtzman, a neurologist who leads a research lab focused on Alzheimer's disease at the Washington University School of Medicine in St. Louis. People would have to be followed for decades after a Covid-19 infection to prove it as a cause, he said. Instead, a Covid-19 infection could cause inflammation that may exacerbate changes that are already happening in the brain, experts say. "The brain has its own immune response to the pathology that's involved in [Alzheimer's] disease progressing," said Holtzman, who was not part of the new study. "When there are other things that cause inflammation that are in the body that can affect the brain, likely what happens is that can even amplify the process that's already going on." Other viruses can cause similar inflammation, experts say. Covid "is another one of the many dozen potential risk factors that I talked about with my patients," said Dr. Richard Isaacson, a neurologist and director of Florida Atlantic Unviersity's Center for Brain Health. He also was not involved in the new study but is a researcher focused on risk prevention for Alzheimer's disease. "I tell people to get a shingles vaccine. I tell people to get their annual flu and Pneumovax," and to exercise and eat a brain-healthy diet. Still, "when there's smoke, there's fire at some point," he said. "I really believe that this is something to at least pay attention to." The latest study, published last week in the Journal of Alzheimer's Disease, found that there were about seven new diagnoses of Alzheimer's disease for every 1,000 seniors who had a documented case of Covid-19 in the past year, compared with about five new diagnoses for every 1,000 who did not. Heather Snyder, vice president of medical and scientific relations at the Alzheimer's Association, notes that broader implications of the pandemic could have played into the study's findings. "The pandemic presented serious delays for individuals seeking out medical diagnoses like Alzheimer's, meaning these results could be driven by those who already had Alzheimer's when they were infected but had not yet sought out a formal diagnosis," she said. The study authors, along with Snyder and other experts, also identify this work as a call for more research on the underlying mechanisms of Alzheimer's disease that might explain the association. In the new study, the diagnosis of Alzheimer's was "mostly tentative," said Dr. Eliezer Masliah, director of the Division of Neuroscience at the National Institutes of Health's National Institute on Aging. Masliah, who was not involved in the study, said that there's evidence that Covid-19 might "trigger cognitive impairment," but there are new ways to confirm the link to Alzheimer's specifically. One next step would be to follow people at risk for Alzheimer's after a Covid-19 infection long-term to track biomarkers found in the blood and brain scans. "In the next couple of years, we're going to have a lot of very important information," Masliah said. And it's an "extremely important problem" to watch, given the scale of disease. "Imagine how many millions of people over the age of 60 or 65, like myself, have had Covid. Say 5% of them or 10% of them or even 1% of them are at risk," he said. "Wow. We're looking at a lot of people in the next few years that might add to the already very large epidemic of Alzheimer's disease that we have." About 6.5 million people over the age of 65 are living with Alzheimer's, according to estimates from the Alzheimer's Association. And it was the seventh leading cause of death in the US in 2020, according to data from the US Centers for Disease Control and Prevention. "Alzheimer's disease is a serious and challenging disease, and we thought we had turned some of the tide on it by reducing general risk factors such as hypertension, heart disease, obesity and a sedentary lifestyle," said Dr. Pamela Davis, a research professor at Case Western Reserve University and co-author of the new study. "Now, so many people in the US have had Covid, and the long-term consequences of Covid are still emerging. It is important to continue to monitor the impact of this disease on future disability."
|
Scooped by
Juan Lama
|
Gene therapy has re-emerged as a potentially revolutionary treatment for familial and, eventually, sporadic, Alzheimer’s disease (Parts 2 and 3 of the Society for Neuroscience 2019 annual meeting series). While researchers are mulling over targets and strategies, what can they learn from gene therapies that are already in, or close to, clinical trials? Dozens of such therapies are being developed for lysosomal dysfunction, which is a feature of Alzheimer’s, Parkinson’s, and frontotemporal dementias (Whyte et al., 2017; Bonam et al., 2019). Could treatments for lysosomal storage disorders help scientists find ways to rid aging cells of proteins that lead to neurodegeneration? It’s clear that cells need well-functioning lysosomes to maintain homeostasis. These acidic organelles are brimming with enzymes ready to break down washed-up proteins, lipids, and carbohydrates that end up inside lysosomes when they fuse with autophagosomes. The little sacs are deceptively complex: a typical lysosome contains around 60 different acid hydrolases alone, cathepsins being perhaps the best-known, plus granulins and other components (Marques and Saftig 2019). Lysosomes degrade Aβ, α-synuclein, and other proteins that accumulate in neurodegenerative disorders (Wang et al., 2012; Shacka et al., 2008). In the AD brain, lysosomes accumulate in neurons, and lysosomal proteins are even found in amyloid plaques (Nixon et al., 1992; Ihara et al., 2012). Since then, a steady clip of papers have documented the importance of lysosomal degradation in age-related neurodegeneration. Some implicated microglia (Paresce et al., 1997; Solé-Domènech et al., 2016). Most recently, single-cell analysis of AD brain tissue pinpointed upregulation of the lysosomal master transcription factor TFEB in astrocytes, where it regulates expression of as many as 10 AD genes (Nov 2019 news). Scientists believe that when lysosomes malfunction in subtle ways, proteins such as Aβ, α-synuclein, and TDP-43 can gradually build up in cells of the aging brain, increasing the chances they will form toxic oligomers or aggregates. But when lysosomes take a severe hit, disease strikes already in childhood. Scientists know of at least nine forms of lysosomal storage disorder, including Niemann-Pick type C, Gaucher, Tay-Sachs, and Fabry diseases. Many have subtypes. The 14 known neuronal ceroid lipofuscinoses, seven mucopolysaccharidoses, five mucolipidoses, and two gangliosidoses are named after the type of molecule whose defective degradation in lysosomes leads to their buildup, i.e., storage. Interestingly for gene-therapy developers, almost all these lysosomal storage diseases are monogenetic, caused by a pathogenic mutation in one or two gene copies encoding an enzyme or protein essential to lysosome function. They tend to start in infancy, childhood, or young adulthood and lead to physical deformities, dementia, motor defects, sometimes blindness, and often an early death (Kohlschütter et al., 2019). ...
|
Amazing
https://buypsychedelicdrugs.com/product-category/dmt/
https://buypsychedelicdrugs.com/product/5-meo-dmt/
https://buypsychedelicdrugs.com/product/4-aco-dmt/
https://buypsychedelicdrugs.com/product/ayahuasca/
https://buypsychedelicdrugs.com/product/changa-dmt/
https://buypsychedelicdrugs.com/product/buy-dmt-vape-pen/
https://buypsychedelicdrugs.com/product/lsd-tabs/
https://buypsychedelicdrugs.com/product/buy-mimosa-hostilis-root-bark-powdered-mhrb/
https://buypsychedelicdrugs.com/product/nn-dmt/
https://buypsychedelicdrugs.com/product/amanita-muscaria/
https://buypsychedelicdrugs.com/product/buy-dragons-dynamite-truffles/
https://buypsychedelicdrugs.com/product/golden-teachers/
https://buypsychedelicdrugs.com/product/buy-high-hawaiians-truffles/
https://buypsychedelicdrugs.com/product/liberty-caps/
https://buypsychedelicdrugs.com/product/buy-microdosing-psilocybin-truffles-10-pack/
https://buypsychedelicdrugs.com/product/buy-microdosing-psilocybin-truffles-2-pack-in-stock/
https://buypsychedelicdrugs.com/product/buy-microdosing-psilocybin-truffles-20-pack/
https://buypsychedelicdrugs.com/product/golden-teachers/
https://buypsychedelicdrugs.com/product/buy-penis-envy-mushroom/
https://buypsychedelicdrugs.com/product/codeine-promethazine/
https://buypsychedelicdrugs.com/product/ecstasy-mdma/
https://buypsychedelicdrugs.com/product/microdosing-psilocybin-truffles-1-pack-for-sale/
https://buypsychedelicdrugs.com/product/mush-rocks-truffles-for-sale/
https://buypsychedelicdrugs.com/product/pcp-powder/
https://buypsychedelicdrugs.com/product/cocaine/
https://buypsychedelicdrugs.com/product/methamphetamine/
https://buypsychedelicdrugs.com/product/xanax/
https://buypsychedelicdrugs.com/product/lsd-gel-tabs/
https://buypsychedelicdrugs.com/product/lsd-liquid/
https://caluaniemuelearoxidizeusa.com/product/buy-10l-caluanie-muelear-pasteurize/
https://caluaniemuelearoxidizeusa.com/product/buy-20l-caluanie-muelear-oxidize/
https://caluaniemuelearoxidizeusa.com/product/buy-5l-caluanie-muelear-pasteurize/
https://caluaniemuelearoxidizeusa.com/product/buy-caluanie-muelear-pasteurize/