A report newly published by the Centers for Disease Control and Prevention estimates that the burden of Alzheimer’s disease and related forms of dementia in the United States will double by the year 2060.
About 5.7 million individuals in the United States are living with Alzheimer’s disease, according to the Alzheimer’s Association.
This neurodegenerative disease is one of the leading causes of disability and the sixth-leading cause of mortality in the U.S.
With annual healthcare costs of more than $250 billion, the disease also puts a significant strain on the nation’s healthcare system.
Researchers at the University of Basel have discovered a factor that could support the early detection of neurodegenerative diseases such as Alzheimer’s or Parkinson’s. This cytokine is induced by cellular stress reactions after disturbances of the mitochondria, the “cell’s power plants,” as neuropathologists write in the journal Cell Reports.
The normal functioning of human cells is based on the coordinated interaction of different cellular organelles. In many cases, an impaired communication between these organelles will lead to the activation of a stress response to ensure the survival of affected cells. A research group was able to demonstrate this in detail for brain neurons. The group is headed by Prof. Dr. Stephan Frank from the Institute of Medical Genetics and Pathology at the University of Basel and University Hospital of Basel; the universities of Cambridge (UK) and Padua (Italy) were also involved.
The neuropathologists were able to show that impairments on the level of mitochondria, commonly known as the “cell’s powerhouses,” also affect neighboring organelles, such as the so-called endoplasmic reticulum. A consecutively activated stress reaction leads to the release of fibroblast growth factor-21 (FGF21) by nerve cells with disturbed mitochondria. The Basel researchers further observed that the same substance is also induced in various models of neurodegenerative disorders, where it can be detected prior to neuronal cell death.
Scientists drilling down to the molecular roots of Alzheimer’s disease have encountered a good news/bad news scenario. A major player is a gene called TREM2, mutations of which can substantially raise a person’s risk of the disease. The bad news is that in the early stages of the disease, high-risk TREM2 variants can hobble the immune system’s ability to protect the brain from amyloid beta, a key protein associated with Alzheimer’s.
The good news, however, according to researchers at Washington University School of Medicine in St. Louis, is that later in the disease, when the brain is dotted with toxic tangles of another Alzheimer’s protein known as tau, the absence of TREM2 protein seems to protect the brain from damage. Mice without TREM2 suffer much less brain damage than those with it.
The findings potentially make targeting the TREM2 protein as a means of preventing or treating the devastating neurodegenerative disease a little more complicated, and suggest that doctors may want to activate TREM2 early in the disease and tamp it down later.
Research led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health New Orleans, has discovered a new class of molecules in the brain that synchronize cell-to-cell communication and neuroinflammation/immune activity in response to injury or diseases. Elovanoids (ELVs) are bioactive chemical messengers made from omega-3 very long chain polyunsaturated fatty acids (VLC-PUFAs,n-3). They are released on demand when cells are damaged or stressed.
“Although we knew about messengers from omega-3 fatty acids such as neuroprotectin D1 (22 carbons) before, the novelty of the present discovery is that elovanoids are made of 32 to 34 carbon atoms in length,” notes Nicolas Bazan, MD, PhD, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health New Orleans. “We expect that these structures will profoundly increase our understanding of cellular cross talk to sustain neuronal circuitry and particularly to restore cell equilibrium after pathological insults.”
A Loyola University Chicago study has found that abnormal proteins found in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease all share a similar ability to cause damage when they invade brain cells.
The finding potentially could explain the mechanism by which Alzheimer’s, Parkinson’s, Huntington’s, and other neurodegenerative diseases spread within the brain and disrupt normal brain functions.
The finding also suggests that an effective treatment for one neurodegenerative disease might work for other neurodegenerative diseases as well.
Psychiatric disorders do not increase the risk of Alzheimer’s disease, according to a recent study from the University of Eastern Finland. However, the prevalence of psychiatric diagnoses increased before the Alzheimer’s diagnosis, which might be due to prodromal symptoms of Alzheimer’s disease. The results were published in European Psychiatry.
History of mood disorder, such as depression, or any psychiatric disorder were associated with a higher risk of Alzheimer’s disease when psychiatric disorders that occurred at least five years before the Alzheimer’s diagnosis were taken into account. However, the associations disappeared when this time window was extended to 10 years. The exponential increase in the prevalence of psychiatric disorders before the diagnosis implies that some of these psychiatric disorders might actually have been prodromal symptoms of Alzheimer’s disease. This underlines the importance of proper differential diagnostics of Alzheimer’s disease. Further, the findings also highlight the importance of using an appropriate time window when assessing the risk factors of neurodegenerative diseases with a long onset period. Otherwise the identified “risk factors” may actually be manifestations of the neurodegenerative disease. It should also be acknowledged that although psychiatric disorders diagnosed 10-40 years before Alzheimer’s disease were not related to a higher risk, the life expectancy of persons with psychiatric disorders was, and is still decreased. Thus, those persons with psychiatric disorders who lived long enough to develop Alzheimer’s disease were a selected sample of all persons with psychiatric disorders.
The older we get, our brain ages. Cognitive abilities decline and the risk of developing neurodegenerative diseases like dementia, Alzheimer’s and Parkinson’s disease or having a stroke steadily increases. A possible cause is the accumulation of iron molecules within neurons, which seems to be valid for all vertebrates. In a collaborative research project within the consortium JenAge, researchers from the Leibniz Institute on Aging — Fritz Lipmann Institute (FLI) in Jena, Germany, and the Scuola Normale Superiore (SNS) in Pisa, Italy, found that this iron accumulation is linked to a microRNA called miR-29. This little molecule has so far been known to act as a tumor suppressor, hindering the proliferation of cancer cells. However, clearly, miR-29 also regulates whether or not iron can be deposited in neurons. Using the African fish Nothobranchius furzeri — the shortest-living vertebrate that can be kept under laboratory conditions — the team of Alessandro Cellerino showed a large increase of iron deposits in fish where miR-29 had been suppressed, which led to premature brain aging. In contrast, healthy fish showed the more miR-29 in their neurons, the older they were. Hence, miR-29 acts as a kind of anti-aging molecule during aging, inhibiting the accumulation of iron in neurons.
New therapeutic approach for the treatment of neurodegenerative diseases and strokes
“We strongly believe that our results are relevant for humans as well,” says Alessandro Cellerino, Professor of Physiology at SNS in Pisa and guest scientist at the FLI, who is one of the study’s leaders. In fact, the link between an increased iron accumulation and neurodegenerative diseases or strokes in humans has been known for some time; there are also results showing a reduced concentration of miR-29 in these diseases. However, it is totally new that miR-29 acts as molecular switch that inhibits iron accumulation. “These results are surprising — and very promising, because the development of miR-29-based pharmaceuticals for cancer therapy is already ongoing. This may offer a head start for the development of new therapies for Parkinson’s or Alzheimer’s disease and for the treatment of strokes as well,” Cellerino adds.
Disabling a part of brain cells that acts as a tap to regulate the flow of proteins has been shown to cause neurodegeneration, a new study from The University of Manchester has found.
The research, which was carried out in mice, focused on the Golgi apparatus — a compartment inside all cells in the body that controls the processing and transport of proteins. It is fundamental for the growth of the cell membrane and also for the release of many types of proteins such as hormones, neurotransmitters and the proteins that make up our skeletons.
Working with Chinese colleagues, the Manchester researchers examined the role of the Golgi apparatus in neurons, or brain cells, and found that mice in which the apparatus was disabled suffered from developmental delay, severe ataxia, and postnatal death.
Alzheimer’s and Parkinson’s disease are classic age-related disorders characterised by the accumulation of sticky protein clumps that over time damage the nervous system to erode mobility or memory. The human suffering they cause, as well as the strain on healthcare, are enormous. But there is hope on the horizon. Chemicals extracted from the prickly pear and brown seaweed, two ubiquitous Mediterranean plants, have been elevated to possible drug candidates to combat the neurodegenerative disease, according to research by scientists from the University of Malta and the Centre National de la Recherche Scientifique (CNRS/University of Bordeaux).
“We have long been screening plants scattered across the Mediterranean for small molecules that interfere with the build-up of toxic protein aggregates. The robust effects of chemicals derived from the prickly pear and brown seaweed confirm that our search has certainly not been in vain,” said study co-author Neville Vassallo, MD, PhD, professor of molecular physiology at the University of Malta School of Medicine and Surgery.
Brain tissue can die as the result of stroke, traumatic brain injury, or neurodegenerative disease. When the affected area includes the motor cortex, impairment of the fine motor control of the hand can result. In a new study published inRestorative Neurology and Neuroscience, researchers found that inosine, a naturally occurring purine nucleoside that is released by cells in response to metabolic stress, can help to restore motor control after brain injury.
Based on evidence from rodent studies, researchers used eight rhesus monkeys ranging in age from 5 to 10 years (approximately equivalent to humans from 15 to 30 years of age). All received medical examinations and motor skills were tested, including video recording of fine motor functions used to retrieve small food rewards. All monkeys were given initial MRI scans to ensure there were no hidden brain abnormalities.