Alzheimer’s disease, a severely debilitating and ultimately fatal brain disorder, affects millions worldwide. To date, clinical efforts to find a cure or adequate treatment have met with dispiriting failure.
The disease is now on an ominous course of expansion, due in part to an aging population, and is poised to become a global health emergency. The enigmatic ailment–first described over 100 years ago–remains the only leading killer without effective treatment, prevention or cure.
In a new study, researchers at the ASU-Banner Neurodegenerative Disease Research Center examine the effects of the disease on the functioning of mitochondria–structures performing a variety of essential tasks, including supplying cells with energy.
The new research reveals that a highly toxic form of beta amyloid protein– known as oligomeric a-beta (OAβ)–disrupts the normal functioning of mitochondria. The result is a fateful cascade of events that appears early in the development of Alzheimer’s disease–decades before the onset of clinical symptoms.
The most promising finding in the new study is that human neuronal cells can be protected from OAβ-induced deterioration of their mitochondria when they are pre-treated with a custom-designed compound, suggesting an exciting avenue for future drug targeting.
“Mitochondria are the major source of energy in brain cells and deficiencies in energy metabolism have been shown to be one of the earliest events in Alzheimer’s disease pathobiology. This study reinforces the toxicity of oligomeric amyloid beta on neuronal mitochondria and stresses the importance for protective compounds to protect the mitochondria from oligomeric amyloid beta toxicity,” said Diego Mastroeni, a lead author of the new study.
Alzheimer’s disease (AD) is a brain disorder that destroys memory and thinking skills over time. It is the most common form of dementia in older adults. There is presently no cure for the condition, though treatment options are available. Today, some 5.3 million Americans live with AD, and it is now the sixth leading cause of death in the United States. The number of older adults who will develop AD is expected to more than triple by 2050.
Geriatrics experts have suggested that exercising can improve brain health in older adults. The World Health Organization (WHO) has recommendations for how much older adults should exercise. They suggest that older adults perform 150 minutes a week of moderate exercise (such as brisk walking), 75 minutes a week of vigorous aerobic training, or a combination of the two types. The WHO also recommends older adults perform muscle-strengthening exercises on at least two or more days a week.
However, not all studies of exercise and older adults have proven the benefits of exercise. We don’t know for sure whether exercise slows mental decline or improves older adults’ ability to think and make decisions.
A team of researchers designed a study to learn whether exercise could delay or improve AD symptoms. They reviewed 19 studies that examined the effect of an exercise training program on cognitive function in older adults who were at risk for or diagnosed with AD. The studies included 1,145 older adults, most of whom were in their mid-to late 70s. Of the participants, 65 percent were at risk for AD and 35 percent had been diagnosed with AD.
The researchers published their findings in the Journal of the American Geriatrics Society.
As the researchers examined the studies, they discovered that older adults who did aerobic exercise by itself experienced a three times greater level of improvement in cognitive function than those who participated in combined aerobic training and strength training exercises. The researchers also confirmed that the amount of exercise WHO recommends for older adults was reinforced by the studies they examined.
High-intensity exercise three times a week is safe for individuals with early-stage Parkinson’s disease and decreases worsening of motor symptoms, according to a new phase 2, multi-site trial led by Northwestern Medicine and University of Colorado School of Medicine scientists.
This is the first time scientists have tested the effects of high-intensity exercise on patients with Parkinson’s disease, the second most common neurodegenerative disorder and the most common movement disorder, affecting more than a million people in the United States.
It previously had been thought high-intensity exercise was too physically stressful for individuals with Parkinson’s disease.
The paper will be published in JAMA Neurology Dec. 11, 2017.
Parkinson’s symptoms include progressive loss of muscle control, trembling, stiffness, slowness and impaired balance. As the disease progresses, it may become difficult to walk, talk and complete simple tasks. Most people who develop Parkinson’s are 60 and older.
“If you have Parkinson’s disease and you want to delay the progression of your symptoms, you should exercise three times a week with your heart rate between 80 to 85 percent maximum. It is that simple,” said co-lead author Daniel Corcos, professor of physical therapy and human movement sciences at Northwestern University Feinberg School of Medicine.
Researchers have developed new single-cell sequencing methods that could be used to map the cell origins of various brain disorders, including Alzheimer’s, Parkinson’s, schizophrenia and bipolar disorder.
By analyzing individual nuclei of cells from adult human brains, researchers at the University of California San Diego, Harvard Medical School and Sanford Burnham Prebys Medical Discovery Institute have identified 35 different subtypes of neurons and glial cells and discovered which of these subtypes are most susceptible to common risk factors for different brain diseases.
“There are multiple theories regarding the roots of various brain diseases. Our findings enable us to narrow down and rank which types of cells in the brain carry the most genetic risk for developing these diseases, which can help drug developers pick better targets in the future,” said Kun Zhang, a professor of bioengineering at the UC San Diego Jacobs School of Engineering and co-senior author of the study.
This work builds off of a previous study published in Science, which Zhang also co-led, in which researchers identified 16 subtypes of neurons in the cerebral cortex. That study was the first large-scale mapping of gene activity in the human brain and provided a basis for understanding the diversity of individual brain cells.
“Our ultimate goal is to produce a complete cell atlas of the human brain,” Zhang said. “Here, we’ve created a fuller and more detailed map than what we’ve done in our previous work.”
In the new study, researchers developed a new generation of single-cell sequencing methods that enabled them to identify additional neuronal subtypes in the cerebral cortex as well as the cerebellum, and even further divide previously identified neuronal subtypes into different classes. The new methods also enabled researchers to identify different subtypes of glial cells, which wasn’t possible in the previous study due to the smaller size of glial cells.
The advance was made possible by combining next-generation RNA sequencing with chromatin mapping–mapping of DNA and proteins in the nucleus that combine to form chromosomes–for more than 60,000 individual neurons and glial cells. The work was published Dec. 11 in Nature Biotechnology.