By 2050, 13.5 million people in the United States will live with Alzheimers disease unless early diagnosis and treatment can delay the onset of the disease. Current treatment centers around slowing the progression of the disease.
In the journal EMBO Molecular Medicine, scientists revealed this week that circulating microscopic nucleotides assembled amino acids that bind directly to messenger ribonucleic acids (mRNAs) can identify cellular imbalance in the brain. These nucleotides, called microRNAs, are easily measured blood proteins that may identify the early risk of Alzheimers disease.
The role of these microRNAs in directing mRNAs to protect the brain from inflammation means that targeting them for therapy could inhibit cellular damage in the brain and delay the onset of dementia.
Verna R. Porter, M.D., commented on the pivotal aspects of this research for Medical News Today. Dr. Porter is a neurologist and the director of programs for dementia, Alzheimers disease, and neurocognitive disorders at Providence Saint Johns Health Center in Santa Monica, CA.
Alzheimers disease is usually diagnosed at a relatively advanced/symptomatic stage of the disease with relatively advanced biomarker/molecular pathology for example, the amyloid deposit in the brain is already well-established. The problem has been that by the time the disease is diagnosed, the current treatments have been essentially ineffective in terms of disease modification.
Dr. Verna R. Porter
The molecular brain changes linked to Alzheimers disease often occur many years before those affected manifest clinical symptoms. Therefore, these researchers designed a model to compare biomarker results in healthy adults with those in people with cognitive decline.
In a multifaceted study, based on the similarities between human and murine neurophysiology, research scientists scored young people aged below 30 years for cognitive function. Then, they identified microRNAs present in the blood that matched their cognitive function. Finally, the scientists linked these microRNAs to larger mRNAs associated with cognitive decline.
Once the researchers had made this connection, they studied microRNAs as possible biomarkers for early cognitive decline.
Aging mice can develop cognitive decline, similar to humans. Therefore, the researchers designed a follow-up experiment measuring these same biomarkers in healthy and aging mice. The scientists could now study the before and after of these microRNA biomarkers, looking for their presence in the blood of both mice that were healthy and those that had cognitive decline.
Dr. Islam, Prof. Fischer, and colleagues from the German Center for Neurodegenerative Diseases and the University Medical Center in Gttingen, Germany, found seven microRNAs frequently linked to age-related cognitive decline in mice. They then correlated these microRNAs to their known functions in human genes, which genome-wide association studies (GWAS) had identified.
The scientists compared their mouse microRNA results with the 709 human genes related to cognitive function in healthy individuals. Three microRNAs that regulate genes in cognitively impaired mice were repeatedly linked to crucial genes in human cognitive function.
To further support their results, the researchers imposed the three microRNAs onto cell cultures of the murine hippocampus, a part of the brain responsible for memory. They confirmed that increased expression of these three microRNAs (directing mRNAs) in cell culture impaired neural function and plasticity the ability of nerves to modify themselves in response to experience and injury.
The scientists then directly measured the three microRNAs present in the brains of cognitively impaired mice and found high levels. Finally, they compared their results with those of prior studies, tentatively linking these microRNAs to neuroinflammation and cellular stress. Dr. Porter summarized:
These researchers noted that circulating microRNAs are linked to cognitive function in young/healthy individuals. Using mouse models, these researchers have identified circulating three-microRNA signatures in the blood, which are increased in patients with mild cognitive impairment (MCI) and suggest an enhanced risk of future conversion from MCI to [Alzheimers disease].
In mice, high levels of the three microRNAs correlated with cognitive decline. But is it possible to extrapolate these results to humans? And could the amount of the three microRNAs predict cognitive impairment before clinical signs of dementia appear?
The researchers studied participants from different age groups in cross-sectional settings. First, they analyzed the plasma of individuals with MCI. In comparison with cognitively healthy people, those living with MCI had significantly increased levels of the microRNAs.
The scientists wondered whether the three microRNAs were higher in people with MCI who go on to develop Alzheimers disease. By analyzing past blood samples, they learned that people with higher levels of the three microRNAs were more likely to progress from stable MCI to Alzheimers disease than those with lower levels.
They also measured the microRNAs in the cerebrospinal fluid of people living with MCI and found significantly elevated levels.
Proposing possible mechanisms in humans, the researchers studied human brain cell cultures, treating them with the three microRNAs. Similar to the previously studied mouse brain cell cultures, they found decreased neuronal synaptic function and increased cellular stress.
So, can we intervene in the function of these elevated three microRNAs and reverse brain cell damage?
The answer is maybe. To test this, the scientists developed an inhibitor of each of the three microRNAs. They injected the three microRNA inhibitors (anti-miRs) into mice with Alzheimers-like pathology, finding that this improved the animals performance in hippocampal-dependent learning strategies, such as escaping from a water maze.
The therapeutic hope is that by targeting these early biomarkers of disease (i.e., targeting all three microRNAs using anti-miRs), we may be able to ameliorate cognitive decline in humans, as has been shown using mouse models.
Dr. Verna R. Porter
The researchers acknowledge that many other complex risk factors likely play a role in Alzheimers disease. Due to this, highly effective therapy may require the regulation of several molecular processes.
MNT queried Dr. Porter on why treatments dealing with the onset of Alzheimers disease have been so elusive. Dr. Porter described how researchers have rigorously studied a protein deposit in the brain, called beta-amyloid, as a potential cause of Alzheimers disease. It seems that beta-amyloid accumulation in the brain may interfere with communication between brain cells in people living with Alzheimers disease. She recounted:
A great deal of research effort has been focused on the amyloid cascade hypothesis of [Alzheimers disease] pathology. The numerous clinical trial failures, utilizing various anti-amyloid therapeutic interventions, have been very disappointing []. It has been suggested that the numerous failed clinical trials that have largely focused on beta-amyloid deposits [indicate] that beta-amyloid may not be the main driver of the disease.
Instead, (the) deposition of beta-amyloid in the brain may be a biological response to some other potential trigger. In this view, beta-amyloid deposits would represent residual scars (after-effects) like the scar that seals a wound, rather than the primary driving process of the disease. It may be that anti-amyloid therapies are simply administered too late in the disease progression.
Newer research is looking more broadly at other potential driving factors of the disease, such as tau protein deposition, and the potential preventive role of lifestyle modifications for example, diet, nutrition, exercise, sleep, and appropriate supplements as another potential way forward in the prevention of the disease.
Tau is a protein involved in brain cell stabilization. In some people living with Alzheimers disease, it is dysfunctional, causing neurofibrillary tangles and disturbing synaptic communication between neurons.
The most promising result of the new study is that the three microRNAs appear to be a suitable, minimally invasive biomarker. They are also easy to measure in routine blood samples even in a finger prick. Moreover, the data support that this three-microRNA-signature test could be a first step in helping detect individuals at risk of cognitive disease.
For people living with cognitive decline, early detection may increase their chances of successful therapeutic intervention with existing treatment or future novel RNA-based approaches targeting the three-microRNA signature.
In conclusion, Dr. Porter noted to MNT:
Presently, there is an urgent need for molecular biomarkers that are minimally invasive, able to detect an individual at risk of developing disease, and [able to] detect biomarkers of disease as early as possible even in the setting of multiple disease pathologies, e.g., mixed Alzheimers and vascular pathology. The hope is that simple approaches, such as a blood test, could be applicable in the context of routine screening approaches with the [aim] of identifying individuals at risk for developing Alzheimers disease, who could then undergo further diagnostic/confirmatory evaluations.
Read this article:
Dementia: Early biomarkers in the blood may predict cognitive decline - Medical News Today
- Copy number variation of the restorer Rf4 underlies human selection ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- NYU Langone Health in the NewsThursday, November 9, 2023 - NYU Langone Health - November 15th, 2023 [November 15th, 2023]
- Eugenics: Plaguing scientific community with dark history | Opinion ... - The Arkansas Traveler - November 15th, 2023 [November 15th, 2023]
- Cranberries can bounce, float and pollinate themselves: The saucy ... - Japan Today - November 15th, 2023 [November 15th, 2023]
- Government Housing Assistance Linked to Increased Cancer ... - HealthDay - November 15th, 2023 [November 15th, 2023]
- Rate of New Lung Cancer Cases Has Decreased Over Last Five Years - HealthDay - November 15th, 2023 [November 15th, 2023]
- Clinically relevant antibiotic resistance genes are linked to a limited ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- Disparities in Guideline-Concordant Care Found for Black CRC ... - HealthDay - November 15th, 2023 [November 15th, 2023]
- Mathematician Heather Harrington is new director at the Max Planck ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- New study finds genetic testing can effectively identify patients with ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- STK11 loss leads to YAP1-mediated transcriptional activation in ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- CRISPR-broad: combined design of multi-targeting gRNAs and ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- Master regulator of the dark genome greatly improves cancer T-cell ... - Science Daily - November 15th, 2023 [November 15th, 2023]
- Omega Therapeutics Showcases Bidirectional and Multiplexed ... - BioSpace - November 15th, 2023 [November 15th, 2023]
- Today is International 15q Day - ASBMB Today - November 15th, 2023 [November 15th, 2023]
- Evolution of taste: Sharks were already able to perceive bitter ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- Stanford Scientists Uncover New Indicators of Health, Disease, and ... - SciTechDaily - October 16th, 2023 [October 16th, 2023]
- NHGRI Director Eric Green elected to the National Academy of ... - National Human Genome Research Institute - October 16th, 2023 [October 16th, 2023]
- Monkey survives for two years after gene-edited pig-kidney transplant - Nature.com - October 16th, 2023 [October 16th, 2023]
- Opinion: Interest in RNA Editing Accelerates as Therapies Approach ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- Regulation of dermal fibroblasts by human neutrophil peptides ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Consistent effects of the genetics of happiness across the lifespan ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Storytelling through the looking glass of genetics The Stute - The Stute - October 16th, 2023 [October 16th, 2023]
- Pet dogs shed light on human health, researchers say - UPI News - October 16th, 2023 [October 16th, 2023]
- Native microbiome dominates over host factors in shaping the ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Illinois-led project to sequence soybean genomes, improve future ... - Herald-Whig - October 16th, 2023 [October 16th, 2023]
- Unrealized targets in the discovery of antibiotics for Gram-negative ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- How Biotech And AI Are Transforming The Human - Noema Magazine - October 16th, 2023 [October 16th, 2023]
- The Many Lives of Alexandria Forbes - BioSpace - October 16th, 2023 [October 16th, 2023]
- CEP20 promotes invasion and metastasis of non-small cell lung ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Genotyping, sequencing and analysis of 140,000 adults from Mexico ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- The role and impact of alternative polyadenylation and miRNA ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Human - Simple English Wikipedia, the free encyclopedia - January 30th, 2023 [January 30th, 2023]
- Deep Dive Ties Together Dog Genetics, Brain Physiology and Behavior to Explain Why Collies Are Different from Terriers - Scientific American - December 12th, 2022 [December 12th, 2022]
- How oxytocin drives connections of newly integrated adult-born neurons: Research - Hindustan Times - December 12th, 2022 [December 12th, 2022]
- Alzheimer's Disease Genetics Fact Sheet - National Institute on Aging - December 2nd, 2022 [December 2nd, 2022]
- Human genetic clustering - Wikipedia - November 23rd, 2022 [November 23rd, 2022]
- Human Genome Project Fact Sheet - November 23rd, 2022 [November 23rd, 2022]
- Abstracts | International Congress of Human Genetics 2023 - November 23rd, 2022 [November 23rd, 2022]
- Ancient DNA and Neanderthals | The Smithsonian Institution's Human ... - November 16th, 2022 [November 16th, 2022]
- Biological Influences on Human Behavior: Genetics & Environment - November 16th, 2022 [November 16th, 2022]
- Fluent BioSciences showcasing breakthrough solutions to enable unprecedented scale, cost-efficiency and access for single-cell RNA sequencing at the... - October 28th, 2022 [October 28th, 2022]
- Human behaviour genetics - Wikipedia - October 23rd, 2022 [October 23rd, 2022]
- Nucleome Therapeutics raises oversubscribed 37.5 million Series A financing to decode the dark matter of the human genome and deliver first-in-class... - October 19th, 2022 [October 19th, 2022]
- Gladstone data scientist elected to the National Academy of Medicine - EurekAlert - October 19th, 2022 [October 19th, 2022]
- Ocugen to Host R&D Day in New York City on Tuesday, November 1, 2022 - Yahoo Finance - October 19th, 2022 [October 19th, 2022]
- Pharmacy researcher earns $2.3 million NIH award to study opioid addiction - EurekAlert - October 19th, 2022 [October 19th, 2022]
- Study shows age often plays a bigger role than genetics in gene expression and susceptibility to disease - Anti Aging News - October 19th, 2022 [October 19th, 2022]
- CSRWire - Direct Relief, Amgen and C/Can Team Up To Improve Access to Breast Cancer Diagnostics and Treatment in Paraguay - CSRwire.com - October 19th, 2022 [October 19th, 2022]
- Maze Therapeutics Appoints Harold Bernstein, M.D., Ph.D., as President, Research and Development and Chief Medical Officer - Business Wire - October 19th, 2022 [October 19th, 2022]
- New Rare Disease Therapy Effectively Lowers Plasma Phe in Patients with PKU - MD Magazine - October 19th, 2022 [October 19th, 2022]
- GSK : announces expanded collaboration with Tempus in precision medicine to accelerate R&D - Marketscreener.com - October 19th, 2022 [October 19th, 2022]
- Famous Scientific Discoveries That Changed the Course of History - 24/7 Wall St. - October 19th, 2022 [October 19th, 2022]
- Construction workers seek fulfilment of their demands - Star of Mysore - October 19th, 2022 [October 19th, 2022]
- Genetics | The Smithsonian Institution's Human Origins Program - October 13th, 2022 [October 13th, 2022]
- Genetics - Wikipedia - October 13th, 2022 [October 13th, 2022]
- Study looking at human genetics and Covid vaccine immune responses - Science Media Centre - October 13th, 2022 [October 13th, 2022]
- ASHG 2022 in Los Angeles brings together researchers from around the world to advance discoveries in genetics, genomics research - EurekAlert - October 13th, 2022 [October 13th, 2022]
- Maze Therapeutics Appoints Harold Bernstein, M.D., Ph.D., as President, Research and Development and Chief Medical Officer - Yahoo Finance - October 13th, 2022 [October 13th, 2022]
- The Age of the Pangenome Dawns - DNA Science - PLOS - October 13th, 2022 [October 13th, 2022]
- Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome - Nature.com - October 13th, 2022 [October 13th, 2022]
- Genome editing technologies: final conclusions of the re-examination of Article 13 of the Oviedo Convention - Council of Europe - October 13th, 2022 [October 13th, 2022]
- Global Biobank Meta-analysis Initiative making genome-wide association studies more diverse and representative - EurekAlert - October 13th, 2022 [October 13th, 2022]
- New NHS genetic testing service could save thousands of children in England - The Guardian - October 13th, 2022 [October 13th, 2022]
- Covid protection may be boosted by genes, study shows - Yahoo News Australia - October 13th, 2022 [October 13th, 2022]
- Genomics in Cancer Care Market is estimated to be US$ 72.61 billion by 2032 with a CAGR of 16.3% during the forecast period 2032 - By PMI -... - October 13th, 2022 [October 13th, 2022]
- Identification of hub genes and candidate herbal treatment in obesity through integrated bioinformatic analysis and reverse network pharmacology |... - October 13th, 2022 [October 13th, 2022]
- Our *Homo sapiens* ancestors shared the world with Neanderthals, Denisovans and other types of humans whose DNA lives on in our genes -... - October 8th, 2022 [October 8th, 2022]
- Blue Eyed People Have a Single Ancestor | History of Yesterday - History of Yesterday - October 6th, 2022 [October 6th, 2022]
- Heart infection could be cause of death of Polish, US hero - ABC News - October 6th, 2022 [October 6th, 2022]
- 23andMe Announces Trials-in-Progress Poster Presentation on 23ME-00610, An Investigational Antibody Targeting CD200R1, at The Society for... - October 6th, 2022 [October 6th, 2022]
- The Genetic Drivers Of Longevity In Mice, Humans And Worms - Science 2.0 - October 6th, 2022 [October 6th, 2022]
- ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma | Communications Biology - Nature.com - October 6th, 2022 [October 6th, 2022]
- 'Neanderthal Man' Nobel Prize winner Svante Pbo revolutionized anthropology. Here is a look back at his groundbreaking 2014 memoir - Genetic Literacy... - October 6th, 2022 [October 6th, 2022]
- Understanding Human Genetic Variation - NCBI Bookshelf - September 14th, 2022 [September 14th, 2022]
- Genetics - National Institute of General Medical Sciences (NIGMS) - September 14th, 2022 [September 14th, 2022]
- People with ME invited to take part in major genetic study - The Independent - September 14th, 2022 [September 14th, 2022]
- Ketamine Promising for Rare Condition Linked to Autism - Medscape - September 14th, 2022 [September 14th, 2022]
- How a small, unassuming fish helps reveal gene adaptations - University of Wisconsin-Madison - September 14th, 2022 [September 14th, 2022]
- How Nutrigenomics Explores Links Between Nutrition And Genes - Health Digest - September 14th, 2022 [September 14th, 2022]