Category: Neurodegenerative Diseases

Categories : Neurodegenerative DiseasesTags :

Protein Synthesis Fix may Reverse Cognitive Decline in Alzheimer’s

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Restoring protein synthesis in the brain may reverse the cognitive decline associated with Alzheimer’s, according to a study by researchers from New York University (NYU) and the Federal University of Rio de Janeiro (UFRJ).

Current Alzheimer’s treatment research focuses on reducing the phenomena linked to the disease, such as amyloid plaques, neurofibrillary tangles, and neuroinflammation. The study aimed to determine whether restoring protein synthesis would also be beneficial.

“The synthesis of new proteins in the brain is essential for proper neuronal function and, notably, for memory consolidation. We and others have previously shown that impairments in brain protein synthesis contribute memory deficits in Alzheimer’s disease model mice, and that the brains of Alzheimer’s patients exhibit clear signs of impaired protein synthesis. We thus asked ourselves whether rescuing brain protein synthesis might be an approach to improve memory function in Alzheimer’s disease,” said co-senior author Sergio Ferreira, a professor at UFRJ.

“Given the complex nature of Alzheimer’s disease, identifying and targeting abnormal molecular pathways that effectively improve cognition has been challenging,” added co-senior author Eric Klann, a professor at NYU. “Our findings show that jump-starting protein synthesis in the brain can revive lost cognitive functions. We hope that this work can serve as a step forward in treating this devastating disease.”

Previous research found that a cellular quality control mechanism called the integrated stress response (ISR) was found to slow down protein synthesis to weed out problems like cancerous cells, but can get stuck in the ‘on’ position. In 2013, a drug called ISRIB was developed to reverse this (ISRIB stands for ISR InhiBitor). 

Previous research with ISRIB had shown positive results in restoring memory function in mice, months after traumatic brain injury (TBI), reversing cognitive impairments in Down Syndrome , preventing noise-related hearing loss, treating certain prostate cancers, and even cognitive enhancement in healthy animals.

The researchers determined that in Alzheimer’s patients, critical components of protein synthesis are depleted in the hippocampus. The researchers hypothesised that some cognitive function could be returned if protein synthesis was restored with ISRIB.  

The researchers used mice with Alzheimer’s-like conditions as a model. Testing the mice’s memory (eg with maze runs), they found memory function and hippocampal protein synthesis restored with ISRB. Restoration of hippocampal neural plasticity and memory functions was observed even in simulated advanced Alzheimer’s. 

The results indicate that restoring protein synthesis with drugs such as ISRIB, could work together towards reversing cognitive decline from Alzheimer’s in humans. 

Source: Medical Xpress

Journal information: “Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease,” stke.sciencemag.org/lookup/doi … 26/scisignal.abc5429

Categories : Ageing Neurodegenerative DiseasesTags :

Obesity Adds to Alzheimer Severity

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In addition to it being a risk factor for many known chronic diseases, obesity is an additional burden on cerebral health and may also be associated with the progression of Alzheimer’s disease, according to a new study from the University of Sheffield and the University of Eastern Finland.  

The study used multimodal neural imaging and showed that obesity may contribute to the vulnerability of neural tissue, while maintaining a healthy weight helped to maintain brain structure in mid dementia Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disease which accounts for two thirds of dementia in over 65s, is the sixth leading cause of death in the United States and there is no cure at present.  

Lead author Professor Annalena Venneri from the University of Sheffield’s Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: “More than 50 million people are thought to be living with Alzheimer’s disease and despite decades of ground breaking studies and a huge global research effort we still don’t have a cure for this cruel disease.

“Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer’s, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease.”

She added that it was important to educate people early on in their lives as it was too late to wait until the 60s to lose weight as the disease lurks in the backgrounds.

The researchers examined MRI scans of the brains of 47 patients diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 individuals who were cognitively healthy. Using three complementary, computational techniques, they studied the brain’s anatomy, blood flow and also the brain’s fibres.

They compared gray matter volume, white matter integrity, cerebral blood flow and obesity. Grey matter volume decreases in Alzheimer’s. In patients with mild Alzheimer’s, an association was found with obesity and grey matter volume around the right temporoparietal junction, suggesting obesity creates a neural vulnerability in cognitively impaired patients. The study also found that maintaining a healthy weight may help preserve brain structure in structure in the presence of age and disease-related weight loss.

Joint author Dr Matteo De Marco from the University of Sheffield’s Neuroscience Institute, said: “Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer’s disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

“We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer’s disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don’t often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure.”

Source: Medical Xpress

Journal information: Manmohi D. Dake et al, Obesity and Brain Vulnerability in Normal and Abnormal Aging: A Multimodal MRI Study, Journal of Alzheimer’s Disease Reports (2021). DOI: 10.3233/ADR-200267

Categories : Ageing Neurodegenerative DiseasesTags :

Parkinson’s Disease Spotted in Advance with Health Checkup

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A study by the University of Nagoya has shown that general health checkups may be effective at spotting early signs of Parkinson’s disease (PD) in advance.

Specifically, the prodromal stage shows sex differences, with the markers for males being decreased cholesterol and haematocrit (the percentage of red blood cells in blood) levels, while in females it is increased blood pressure. PD is the second most common disease affecting the nervous system after Alzheimer’s disease, is caused by a deficiency in the neurotransmitter dopamine. By the stage where sufferers experience motor symptoms such as tremors, stiffness, bradykinesia (slowness of movement), more than half of all dopaminergic neurons have been lost. Postural instability occurs in the late stage. Several processes have been implicated in PD, such as mitochondrial dysfunction, defective protein clearance mechanisms, and neuroinflammation, but it is not clear how these factors interact.

Prior studies have shown that non-motor symptoms including constipation, rapid eye movement sleep behaviour disorder, impairment of sense of smell, and depression, emerge in patients with PD 10 to 20 years before the onset of motor symptoms – meaning that PD may be detectable in advance with other measures.

“If we can detect biological changes in the patients’ bodies well before the onset of the motor symptoms, we can start medical treatments in an early stage,” said Prof Masahisa Katsuno of the Graduate School of Medicine at Nagoya University.

The team used health checkup data from 22 male and 23 female patients with PD, dating to before they were diagnosed with the disease. They supplemented this with data from 60 male and 60 female healthy individuals who had checkup data for at least four years.The checkup data was compared between healthy individuals and PD patients to establish a baseline, and then were examined for longitudinal changes prior to the onset of PD. They found that in the premotor stage, blood pressure increased in females, while in males total and low-density cholesterol levels and haematocrit decreased.

“In this study, we found that blood pressure, haematocrit, and serum cholesterol levels are potential biomarkers of Parkinson’s disease before the onset of its motor symptoms,” said Prof Katsuno. “This finding indicates that general health checkups can help detect early signs of developing Parkinson’s disease.”  Based on the findings, the team is now working to identify individuals at risk of developing PD in an attempt to forestall the development of their disease.

Source: Medical Xpress

Journal information: Katsunori Yokoi et al. Longitudinal analysis of premotor anthropometric and serological markers of Parkinson’s disease, Scientific Reports (2020). DOI: 10.1038/s41598-020-77415-1

Categories : Gastrointestinal Neurodegenerative DiseasesTags :

Gut Immune Cells Protect The Brain in MS Flare-ups

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Scientists from the University of California, San Francisco, have observed gut immune cells moving up out of the gastrointestinal tract to the brain during multiple sclerosis (MS) flareups, where they seem to exert some protective effects.

In MS, other immune cells attack the myelin sheath, resulting in flare-ups, where they experience memory problems, vision loss, pain and other problems. These flare-ups subside after some days, but it is not known why the disease switches back and forth between flare-up and remission.

The new research revealed that the flare-ups were brought under control with the unlikely assistance of gut immune cells, which produce Immunoglobulin-A (IgA) and act as the immune system’s first line of defence in the GI tract. Some of these cells actually leave the gut and migrate to the brain, where it appears they reduce inflammation.

“It was a very new idea,” said lead author, Sergio Baranzini, PhD, neurology professor at the UCSF Weill Institute for Neurosciences, . “Nobody thought to look for this type of immune cell.”

The gut immune cells were found only in cerebrospinal fluid of MS sufferers when they experienced a flare-up, and not in remission. Recent research indicated that an unhealthy GI microbiome was involved in MS, and the researchers determined that these immune cells only attacked potentially damaging bacteria, not the myelin sheath.

It is anticipated that this discovery may bring insights into new therapies to treat the disease. 

Source: Medical Xpress