People with blood type AB may be more likely to develop memory loss in later years than people with other blood types, according to a study published by Kristine Alexander, Ph.D., postdoctoral fellow in medicine, Mary Cushman, M.D., M.Sc., professor of medicine at the University of Vermont College of Medicine, and colleagues.

AB is the least common blood type, found in only about four percent of the U.S. population. The study found that people with AB blood were 82 percent more likely to develop the thinking and memory problems that can lead to dementia than people with other blood types. Previous studies have shown that people with type O blood have a lower risk of heart disease and stroke, factors that can increase the risk of memory loss and dementia.

The study was part of a larger study (the REasons for Geographic And Racial Differences in Stroke, or REGARDS Study) of more than 30,000 people followed for an average of 3.4 years. In those who had no memory or thinking problems at the beginning, the study identified 495 participants who developed thinking and memory problems, or cognitive impairment, during the study. They were compared to 587 people with no cognitive problems.

People with AB blood type made up 6 percent of the group who developed cognitive impairment, which is higher than the 4 percent found in the population.

“Our study looks at blood type and risk of cognitive impairment, but several studies have shown that factors such as high blood pressure, high cholesterol and diabetes increase the risk of cognitive impairment and dementia,” says Alexander. “Blood type is also related to other vascular conditions like stroke, so the findings highlight the connections between vascular issues and brain health. More research is needed to confirm these results.”

In the study, researchers also looked at blood levels of factor VIII, a protein that helps blood to clot. High levels of factor VIII were related to higher risk of cognitive impairment. People in this study with higher levels of factor VIII were 24 percent more likely to develop thinking and memory problems than people with lower levels of the protein. People with AB blood had a higher average level of factor VIII than people with other blood types.

“For stroke, we found that about half of the association of blood type AB with stroke was due to differences between people in levels of clotting Factor VIII, but our current study of cognitive impairment did show this finding,” says Cushman, who adds that the differences in the findings of the two studies suggests that other reasons – not yet understood – are likely playing a role in explaining the impact on of blood type AB on cognitive function. Further research is needed to determine those details. University of Vermont

A new Moffitt Cancer Center study shows that counselling from a genetic health care provider before genetic testing educates patients and may help reduce unnecessary procedures.

Up to 10 percent of cancers are inherited, meaning a person was born with an abnormal gene that increases their risk for cancer. ‘Pre-test genetic counselling in which a health care provider takes a thorough family history and discusses the potential risks and benefits of genetic testing is standard of care as recommended by the American Society of Clinical Oncology and National Society of Genetic Counselors,’ said Tuya Pal, M.D., a board-certified geneticist at Moffitt and senior author of the paper.

In the Moffitt study, researchers surveyed 473 patients who had genetic testing for BRCA1 and BRCA2 gene mutations, which are associated with an increased risk of breast and ovarian cancers. Among study participants who saw a board-certified geneticist or genetic counsellor, almost all recalled having a pre-test discussion, compared to only 59 percent of those who did not. These findings suggest large differences in quality of care across providers who order testing.

The researchers also suggest there may be cost-of-care implications when genetic health care providers are involved. ‘Our results suggest that genetic health care providers are less likely to order more expensive comprehensive genetic testing, when less expensive testing may be appropriate,’ said Deborah Cragun, Ph.D., lead study author and post-doctoral fellow at Moffitt. ‘Our study found that in cases where less expensive testing may be appropriate, genetic health care providers ordered comprehensive testing for 9.5 percent of participants, compared to 19.4 percent when tests were ordered by other health care providers. At the time of data collection, comprehensive genetic testing cost approximately $4,000, compared to $400 for the less expensive testing.’

The findings are important, noted researchers, because costs and quality of care are often the focus of policy-level decisions in health care. Moffitt Cancer Center

It is something of an eternal question: Can we slow or even reverse the aging process? Even though genetic manipulations can, in fact, alter some cellular dynamics, little is known about the mechanisms of the aging process in living organisms.

Now scientists from the Florida campus of The Scripps Research Institute (TSRI) have found in animal models that a single gene plays a surprising role in aging that can be detected early on in development, a discovery that could point toward the possibility of one day using therapeutics, even some commonly used ones, to manipulate the aging process itself.

“We believe that a previously uncharacterized developmental gene known as Spns1 may mediate the aging process,” said Shuji Kishi, a TSRI assistant professor who led the study.

Using various genetic approaches to disturb Spns1 during the embryonic and/or larval stages of zebrafish—which have emerged as a powerful system to study diseases associated with development and aging—the scientists were able to produce some models with a shortened life span, others that lived long lives.

While most studies of “senescence”—declines in a cell’s power of division and growth—have focused on later stages of life, the study is intriguing in exploring this phenomenon in early stages. “Mutations to Spns1 both disturbs developmental senescence and badly affects the long-term bio-chronological aging process,” Kishi said.

The new study shows that Spns1, in conjunction with another pair of tumour suppressor genes, beclin 1 and p53 can, influences developmental senescence through two differential mechanisms: the Spns1 defect was enhanced by Beclin 1 but suppressed by ‘basal’ p53. In addition to affecting senescence, Spns1 impedes autophagy, the process whereby cells remove unwanted or destructive proteins and balance energy needs during various life stages.

Building on their insights from the study, Kishi and his colleagues noted in the future therapeutics might be able influence aging through Spns1. He noted one commonly used antacid, Prilosec, has been shown to temporarily suppress autophagic abnormality and senescence observed in the Spns1 deficiency.

Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.

The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travellers adjust to time differences more quickly. The results can point to treatment strategies for sleep problems caused by a variety of disorders.

“It’s possible that the severity of many dementias comes from sleep disturbances,” says Satchidananda Panda, a Salk associate professor who led the research team. “If we can restore normal sleep, we can address half of the problem.”

Every cell in the body has a “clock” – an abundance of proteins that dip or rise rhythmically over approximately 24 hours. The master clock responsible for establishing these cyclic circadian rhythms and keeping all the body’s cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brain’s hypothalamus.

More so than in other areas of the brain, the SCN’s neurons are in close and constant communication with one another. This close interaction, combined with exposure to light and darkness through vision circuits, keeps this master clock in sync and allows people to stay on essentially the same schedule every day. The tight coupling of these cells also helps make them collectively resistant to change. Exposure to light resets less than half of the SCN cells, resulting in long periods of jet lag.

In the new study, researchers disrupted the light-dark cycles in mice and compared changes in the expression of thousands of genes in the SCN with other mouse tissues. They identified 213 gene expression changes that were unique to the SCN and narrowed in on 13 of these that coded for molecules that turn on and off other genes. Of those, only one was suppressed in response to light: Lhx1.

“No one had ever imagined that Lhx1 might be so intricately involved in SCN function,” says Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. Lhx1 is known for its role in neural development: it’s so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light-dark cycle genes.

By recording electrical activity in the SCN of animals with reduced amounts of the Lhx1 protein, the researchers saw that the SCN neurons weren’t in sync with one another, despite appearing rhythmic individually.

“It was all about communication–the neurons were not talking to each other without this molecule,” says Ludovic Mure, a postdoctoral researcher and an author on the paper. A next step in the work will be to understand exactly how Lhx1 affects the expression of genes that creates this synchronicity.

Studying a mouse version of jet lag–an 8-hour shift in their day-night cycle–the scientists found that those with little or no Lhx1 readjusted much faster to the shift than normal mice. This suggests that because these neurons are less in sync with one another, they are more easily able to shift to a new schedule, though it is difficult for them to maintain that schedule, Panda says.

These mice also exhibited reduced activity of certain genes, including one that creates vasoactive intestinal peptide or Vip, a molecule that has important roles in development and as a hormone in the intestine and blood. In the brain, Vip affects cell communication, but nobody had known that Lhx1 regulated it until now, Panda says. Interestingly, the team also found that adding Vip restored cell synchrony in the SCN.

“This approach helped us to close that knowledge gap and show that Vip is a very important protein, at least for SCN,” Panda says. “It can compensate for the loss of Lhx1.”

On the other hand, cutting back on Vip could be another way to treat jet lag. Vip could be an even easier drug target compared with Lhx1 because Vip is secreted from cells rather than inside cells, Panda says. “If we find a drug that will block the Vip receptor or somehow break down Vip, then maybe that will help us reset the clock much faster,” he adds. Salk Institute for Biological Studies

Autopsies have revealed that some individuals develop the cellular changes indicative of Alzheimer’s disease without ever showing clinical symptoms in their lifetime.
Vanderbilt University Medical Center memory researchers have discovered a potential genetic variant in these asymptomatic individuals that may make brains more resilient against Alzheimer’s.
‘Most Alzheimer’s research is searching for genes that predict the disease, but we’re taking a different approach. We’re looking for genes that predict who among those with Alzheimer’s pathology will actually show clinical symptoms of the disease,’ said principal investigator Timothy Hohman, Ph.D., a post-doctoral research fellow in the Center for Human Genetics Research and the Vanderbilt Memory and Alzheimer’s Center.
The researchers used a marker of Alzheimer’s disease found in cerebrospinal fluid called phosphorylated tau. In brain cells, tau is a protein that stabilises the highways of cellular transport in neurons. In Alzheimer’s disease tau forms ‘tangles’ that disrupt cellular messages.
Analysing a sample of 700 subjects from the Alzheimer’s Disease Neuroimaging Initiative, Hohman and colleagues looked for genetic variants that modify the relationship between phosphorylated tau and lateral ventricle dilation — a measure of disease progression visible with magnetic resonance imaging (MRI). One genetic mutation (rs4728029) was found to relate to both ventricle dilation and cognition and is a marker of neuroinflammation.
‘This gene marker appears to be related to an inflammatory response in the presence of phosphorylated tau,’ Hohman said.
‘It appears that certain individuals with a genetic predisposition toward a ‘bad’ neuroinflammatory response have neurodegeneration. But those with a genetic predisposition toward no inflammatory response, or a reduced one, are able to endure the pathology without marked neurodegeneration.’
Hohman hopes to expand the study to include a larger sample and investigate gene and protein expression using data from a large autopsy study of Alzheimer’s disease.
‘The work highlights the possible mechanism behind asymptomatic Alzheimer’s disease, and with that mechanism we may be able to approach intervention from a new perspective. Future interventions may be able to activate these innate response systems that protect against developing Alzheimer’s symptoms,’ Hohman said. EurekAlert