Category Archives: Research News (General)

A team has developed a system to model Huntington’s in human embryonic stem cells for the first time. In a report published in Development, they describe early abnormalities in the way Huntington’s neurons look, and how these cells form larger structures that had not previously been associated with the disease.

Huntington’s is one of the few diseases with a straightforward genetic culprit: One hundred percent of people with a mutated form of the Huntingtin (HTT) gene develop the disease. The mutation takes the form of extra DNA, and causes the gene to produce a longer-than-normal protein.

Research on Huntington’s has thus far relied heavily on animal models of the disease. Suspecting that the disease works differently in humans, the researchers developed a cell-based human system for their research. They used the gene editing technology CRISPR to engineer a series of human embryonic stem cell lines, which were identical apart from the number of DNA repeats that occurred at the ends of their HTT genes.

When cells divide, they typically each retain one nuclei. However, some of these mutated cells flaunted up to 12 nuclei—suggesting that neurogenesis, or the generation of new neurons, was affected.

Treatments for Huntington’s have typically focused on blocking the activity of the mutant HTT protein. However, this research shows that the brain disruption may actually be due to a lack of HTT protein activity. The researchers created cell lines that completely lacked the HTT protein. These cells turned out to be very similar to those with Huntington’s pathology, corroborating the idea that a lack of the protein—not an excess of it—is driving the disease.

Article:  “Chromosomal instability during neurogenesis in Huntington’s disease.”
Reprinted from materials provided by Rockefeller University.

People with Alzheimer’s disease are known to have disturbances in their internal body clocks that affect sleep/wake cycle and may increase their risk of developing the disorder. Now, new research published in JAMA Neurology indicates that such circadian rhythm disruptions also occur much earlier in people whose memories are intact but whose brain scans show early, preclinical evidence of Alzheimer’s disease.

Previous studies conducted in people and in animals have found that levels of amyloid fluctuate in predictable ways during the day and night. Amyloid levels decrease during sleep, and several studies have shown that levels increase when sleep is disrupted or when people don’t get enough deep sleep.

The researchers tracked circadian rhythms in 189 cognitively normal, older adults with an average age of 66. Of the participants, 139 had no evidence of the amyloid protein that signifies preclinical Alzheimer’s. Most had normal sleep/wake cycles, although several had circadian disruptions that were linked to advanced age, sleep apnea or other causes.

But among the other 50 subjects — who either had abnormal brain scans or abnormal cerebrospinal fluid — all experienced significant disruptions in their internal body clocks, determined by how much rest they got at night and how active they were during the day. Disruptions in the sleep/wake cycle remained even after the researchers statistically controlled for sleep apnea, age and other factors.

By tracking activity during the day and night, the researchers could tell how scattered rest and activity were throughout 24-hour periods. Subjects who experienced short spurts of activity and rest during the day and night were more likely to have evidence of amyloid buildup in their brains, the researchers said.

Paper: “Circadian Rest-Activity Pattern Changes in Aging and Preclinical  Alzheimer Disease”
Reprinted from materials provided by Washington University School of Medicine.

A new study published in Scientific Reports shows that low levels of alcohol consumption may tamp down inflammation and help the brain clear away toxins, including those associated with Alzheimer’s disease.

The research focused on the glymphatic system, the brain’s unique cleaning process that was first described by the same researchers in 2012. They showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste, including the proteins beta amyloid and tau that are associated with Alzheimer’s disease and other forms of dementia. Subsequent research has shown that the glymphatic system is more active while we sleep, can be damaged by stroke and trauma, and improves with exercise.

The new study, which was conducted in mice, looked at the impact of both acute and chronic alcohol exposure.  When they studied the brains of animals exposed to high levels of alcohol over a long period of time, the researchers observed high levels of a molecular marker for inflammation, particularly in cells called astrocytes which are key regulators of the glymphatic system.  They also noted impairment of the animal’s cognitive abilities and motor skills.

Animals that were exposed to low levels of alcohol consumption, analogous to approximately 2 ½ drinks per day, actually showed less inflammation in the brain and their glymphatic system was more efficient in moving CSF through the brain and removing waste, compared to control mice who were not exposed to alcohol.  The low dose animals’ performance in the cognitive and motor tests was identical to the controls.

Paper: “Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.”

Reprinted from materials provided by the University of Rochester Medical Center

Directly involving the thousands of family members and friends who serve as ‘informal carers’ for people with dementia in the evaluation of patients’ symptoms and behaviour could offer improved insights for healthcare professionals and help alleviate feelings of stress, guilt and isolation felt by many who fulfil these duties, a new study published in Dementia has found.

The findings highlight a need for more structured educational programmes covering broader knowledge around the disease for informal carers, who often have no formal training or support networks to depend on. Information on disease progression, guidelines on dealing with challenging behaviours and financial and legal advice could better prepare carers about what to expect.

The research, conducted by an inter-disciplinary team of experts, collated insights from carers and health care professionals and identified key themes which capture the main challenges faced by carers, as well as the type of support they want from health care services.

Previous research found that informal caregivers of people with dementia often display increased levels of depression and stress as well as poor self-rated health.

The new findings show that existing health and social care services are often fragmented which can make communication between healthcare professionals and care providers difficult. Healthcare professionals also stated that while they have a theoretical knowledge of the disease, they felt they often lack knowledge of how it is to live with dementia which can make it difficult to know how best to support caregivers.

The researchers say they hope that the findings will lead to improvements in dementia care with a goal of creating a better educational package for carers.

Paper: “Caregivers’ interactions with health care services – Mediator of stress or added strain? Experiences and perceptions of informal caregivers of people with dementia – A qualitative study”
Reprinted from materials provided by the University of Lincoln.

Increasing the amount of social interaction for people with dementia living in care homes to just one hour a week improves quality of life when combined with personalised care, according to a new study.

A large-scale trial  found that the approach also saves money.

Previous research has found that in many care homes, residents have as little as two minutes of social interaction per day.

The new research, published in PLOS Medicine, upskilled key care home staff to deliver person-centred care. That involves simple measures such as talking to residents about their interests and involving them in decisions around their own care.

When combined with just one hour a week of social interaction, the programme improved quality of life and reduced agitation and aggression in people with dementia.

The trial involved more than 800 people with dementia across 69 care. Two ‘care staff champions’ at each home were trained over four day-long sessions to take simple measures that such as involve talking to residents about their interests and decisions around their own care. Importantly, the approach also saved money compared to standard care.  Researchers say the next key challenge is to roll the programme out across care homes to benefit the lives of people with dementia living in these facilities.

Paper: “Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: A cluster-randomised controlled trial”
Reprinted from materials provided by University of Exeter.

After more than a decade of research, this much we know: it’s good for your brain to know another language.

A new study, published in Neuropsychologia,  goes further, however, focusing specifically on the effects of knowing a second language for patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

Unlike previous studies using CT scans, the researchers  used high-resolution, whole-brain MRI data and sophisticated analysis techniques to investigate language and cognition control areas in the frontal regions of the brain, and medial temporal lobe structures that are important for memory and are brain areas known to atrophy in MCI and AD patients.

Their sample included 34 monolingual MCI patients, 34 multilingual MCI patients, 13 monolingual AD patients and 13 multilingual AD patients.

The researchers say that their findings suggest that multilingualism is associated with increased brain plasticity and cognitive reserve. Moreover, their study indicates, they say, that people who speak more than one language may in some circumstances compensate for AD-related tissue loss by accessing alternative networks or other brain regions for memory processing, a hypothesis they hope to test in future studies.

Paper: “Structural brain differences between monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve”
Reprinted from materials provided by Concordia University.

Scientists developing a rapid, practical test for the early diagnosis of prion diseases have modified the assay to offer the possibility of improving early diagnosis of Parkinson’s disease and dementia with Lewy bodies.

The findings were published in Acta Neuropathologica Communications.

The group tested 60 cerebral spinal fluid samples, including 12 from people with Parkinson’s disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 of whom had Alzheimer’s disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson’s disease and dementia with Lewy bodies with 93 percent accuracy.

Importantly, test results were available within two days, compared to related assays that require up to 13 days. The group conducted the tests using Real-Time Quaking-Induced Conversion (RT-QuIC), an assay developed and refined over the past decade.

Multiple neurological disorders, including Parkinson’s disease and dementia with Lewy bodies, involve the abnormal clumping of a protein called alpha-synuclein into brain deposits called Lewy bodies. The pathological processes in these diseases resemble prion diseases in mammal brains. Like prion diseases, Parkinson’s disease and dementia with Lewy bodies result in progressive deterioration of brain functions.

The researchers continue to adapt the RT-QuIC assay to detect additional types of neurological diseases with greater accuracy using the least invasive patient sample possible—whether that is blood, skin, nasal brushings, or other samples. The group also has trained many international colleagues to use and advance the test.

Article: “Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC” 
Reprinted from materials provided by NIH/National Institute of Allergy and Infectious Diseases.

Low muscle strength during the later teen years has been identified as a risk factor for much later onset of the neurological disease known as ALS, or amyotrophic lateral sclerosis.

A study published in the Journal of Neurology also links low blood counts at a young age to ALS.

The researchers studied Swedish military enlistment data for more than 1.8 million (1,819,817) men in the 1968-2005 period as well as data from the Swedish health care register and mortality register. The majority were 18 years old at the time of enlistment. The follow-up time was up to 46 years.

The group included 526 individuals who developed ALS, a disease that usually occurs after age 50 and involves a successive degradation of the nerves that control muscles. There is no cure, and in most cases patients die after two to five years.

The current study confirms the impression that ALS can be associated with a relatively low body mass index (BMI), even at a young age. The differences, however, were not dramatic. Those who developed ALS had an average BMI of 21.1, compared with 21.9 for the group as a whole.

What stood out instead was the finding that ALS could be associated with low blood counts at military enlistment – in other words, a low proportion of oxygen-carrying red blood cells in the blood. A link was also found between ALS and measured muscle strength in the hands, arms and legs at the time of enlistment.

Paper: “Risk factors in Swedish young men for amyotrophic lateral sclerosis in adulthood”
Reprinted from materials provided by the University of Gothenburg.

With the aid of a PET camera, researchers have developed a new method for investigating the dopamine system in the brains of patients suffering from Parkinson’s disease. The method measures levels of a protein called dopamine transporter and could lead to improved diagnosis of Parkinson’s disease. The study was published in Movement Disorders.

Dopamine is a substance produced in the brain and is responsible for controlling our movements. In Parkinson’s disease, dopamine cells degenerate and their loss is responsible for the motor symptoms that characterise the disorder, such as shaking, slowness of movement and difficulty walking.

Using Positron Emission Tomography (PET), a group of researchers have measured the levels of the dopamine transporter protein DAT that regulates the levels of dopamine in the brain. DAT functions as a biomarker for dopamine cells and is present on the surface of the dopamine cells in the cell bodies, on the nerve fibres and on the nerve endings. By measuring where DAT is found, researchers have been able to map the presence of dopamine cells.

The study was based on 20 patients suffering from mild Parkinsonism and an equal number of healthy individuals. The results showed significantly lower amounts of DAT in nerve endings in the Parkinson’s patients than those not suffering from the disease.

Future studies will examine patients with more advanced Parkinson’s, in order to gain a greater understanding of the links between DAT and clinical variables such as motor symptoms and the various stages of the disease.

Paper: “Nigrostriatal dopamine transporter availability in early Parkinson’s disease”
Reprinted from materials provided by Karolinska Institutet.

A team of researchers has found that gradually depleting an enzyme called BACE1 reverses the formation of amyloid plaques in the brains of mice with Alzheimer’s disease, thereby improving the animals’ cognitive function. The study was published in the Journal of Experimental Medicine.

An early event in Alzheimer’s is the abnormal buildup of beta-amyloid peptide, which can form large amyloid plaques in the brain and disrupt the function of neuronal synapses. BACE1 helps produce beta-amyloid peptide by cleaving amyloid precursor protein (APP).

Researchers have hypothesized that inhibiting BACE1 could keep the plaques from appearing. However, BACE1 controls many important processes by cleaving proteins other than APP, and mice completely lacking BACE1 have been shown to suffer severe neurodevelopmental defects.  For this study, the researchers  generated mice that gradually lose this enzyme as they grow older. These mice were shown to develop normally and appeared to remain perfectly healthy over time.

The researchers then bred these rodents with Alzheimer’s mice. The resulting offspring also formed plaques at this age, even though their BACE1 levels were approximately 50% lower than normal. Remarkably, however, the plaques began to disappear as the mice continued to age and lose BACE1 activity, until, at 10 months old, the mice had no plaques in their brains at all.

Decreasing BACE1 activity also resulted in lower beta-amyloid peptide levels and reversed other hallmarks of Alzheimer’s disease, such as the activation of microglial cells and the formation of abnormal neuronal processes.

Loss of BACE1 also improved the learning and memory of mice with Alzheimer’s disease. However, when the researchers made electrophysiological recordings of neurons from these animals, they found that depletion of BACE1 only partially restored synaptic function, suggesting that BACE1 may be required for optimal synaptic activity and cognition.

Article: “BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions”
Reprinted from materials provided by Rockefeller University.