New dating of cave art reveals history of Puerto Rican people

New research presented at GSA Connects 2023

Meeting Announcement

GEOLOGICAL SOCIETY OF AMERICA

 

IMAGE: 

CAVE ART CAN SOMETIMES INCLUDE TWO DIFFERENT TIMES OF CREATION. IN THIS IMAGE, THE DARKER LIZARD IS A YOUNGER DRAWING THAN THE SUN THAT IS DRAWN BENEATH IT.

view more 

CREDIT: A. ACOSTA-COLON.

17 October 2023
The Geological Society of America
Release No. 23-40
Contact: Justin Samuel
+1-303-357-1026
jsamuel@geosociety.org

For Immediate Release

Leer en español.

Contributed by Sarah Derouin

Pittsburgh, Pa., USA: In the karstic caves of Puerto Rico, cave art paints the rock walls. Previous research has assigned ages to this art based on the ages of nearby archaeological artifacts within the caves, but these ages are relative and may not reflect the true timing of the art creation.

Now, a new study to be presented Wednesday at the Geological Society of America’s GSA Connects 2023 meeting shows that researchers have refined the age of this rupestrian art by dating the pigment in the drawings. Angel Acosta-Colon, a geophysicist at University of Puerto Rico (UPR) at Arecibo, will present the findings.

In Puerto Rican caves, there are three types of art: petroglyphs (carved into the rock), pyroglyphs (drawn from the burnt remnants of objects), and pictographs, or cave drawings. Acosta-Colon says these pictograph drawings are in organic black material, perfect for radiocarbon dating.

Acosta-Colon and his colleague Reniel Rodríguez, an archaeologist at UPR Utuado, visited 11 different caves on La Isla Grande, the big island of the Puerto Rican archipelago. From these caves, they sampled 61 pigments in pictographic art.

The researchers were thoughtful about which art to sample, sampling art that is commonly seen and not unique. “[The pictographs] are not an infinite resource—they are limited,” explains Acosta-Colon. “So if we touch one, we touch it forever and for the future generations, we are not allowing the pleasure of seeing what we see.”

They were also conservative about how much of the material they collected, as sampling destroys a small area of the art. Acosta-Colon says that they take 1 to 2 mg samples from the black markings on cave walls for their analyses.

They ran the microsamples through the Center for Applied Isotope Studies (AIS) at the University of Georgia to get carbon-14 ages for the artwork. The earliest pictographs of abstract, geometrical shapes were dated to ca. 700–400 BCE, coinciding with the Archaic Age.

“That is very important to us because when the European Invasion came to Puerto Rico, they put in a document that our precolonial population was only there for 400 to 500 years,” says Acosta-Colon. “So this proves that we were here [thousands] of years before the European Invasion, and that is documented in science, not context archeology.”

They found that more anthropological-type drawings—with simple shapes of human bodies—were drawn between 200 and 400 CE. “We have gaps of time and that's interesting because we don't know what happened,” says Acosta-Colon, adding that they could fill those gaps with more sampling around the island.

The research team also found more detailed human and animal drawings that were created between 700 and 800 CE. These types of drawings continued throughout the next century, extending through European colonization (around 1500 CE), and include images of horses, ships, and other animals.

Within the array of animals, they discovered a particularly unusual find. “We have an image that looks like a lion—but in Puerto Rico, we don’t have lions,” says Acosta-Colon. When he and Rodriguez considered who could have seen a lion, they thought about the slaves that were brought to the island by the Spanish.

The idea, he notes, is controversial. “But the age of the art is around 1500,” he says. “We have data to corroborate what, I think, is one of the first slave art in caves in Puerto Rico.”

Understanding when these pictographs were created helps explain the history of the Puerto Rican people, says Acosta-Colon. “Normally we get the European history version of Puerto Rico, but this is direct evidence that the story in Puerto Rico didn’t start with the European Invasion, it started much, much earlier in history,” he notes.

He believes that studying more cave art sites may push back the human history record to 5000 BCE. This art, along with archeological finds, can reconstruct the “history of our people, from Archaic people, to the Taino people to the pre-Columbian time.

CAPTION

Over time, the cave art transitioned from more basic geometric shapes, to detailed images of recognizable animals, like this sting ray.

Angel Acosta-Colon (shown here) poses with a number of pictographs, including an unusual find—an animal that looks like a lion. He speculates that this may be the first cave art drawn by slaves that were brought to the island during Spanish colonization.

CREDIT

Credit: A. Acosta-Colon.

Radiocarbon dating of cave pictographic rock art in Puerto Rico

Contact: Angel Acosta-Colon, angel.acosta2@upr.edu
208: D11. Recent Advances in Geoarchaeology: Studies from Asia, Europe and the Americas
Wed., 18 Oct. 2023, 10:20–10:35 a.m.

The Geological Society of America (https://www.geosociety.org) unites a diverse community of geoscientists in a common purpose to study the mysteries of our planet (and beyond) and share scientific findings. Members and friends around the world, from academia, government, and industry, participate in GSA meetings, publications, and programs at all career levels, to foster professional excellence. GSA values and supports inclusion through cooperative research, public dialogue on earth issues, science education, and the application of geoscience in the service of humankind.

###

 

Founder personality could predict start-up success: study

Research shows start-up founders have distinct personality traits, and they’re more important to the success of their companies than previously thought.

Peer-Reviewed Publication

UNIVERSITY OF NEW SOUTH WALES

The stats don’t lie – the overwhelming majority of start-up companies fail. So, what makes the seemingly lucky few not only survive, but thrive?

While good fortune and circumstances can play a part, new research reveals that when it comes to start-up success, a founder’s personality – or the combined personalities of the founding team - is paramount. The study, published today in Scientific Reports, shows founders of successful start-ups have personality traits that differ significantly from the rest of the population – and that these traits are more important for success than many other factors.

“We find that personality traits don’t simply matter for start-ups – they are critical to elevating the chances of success,” says Paul X. McCarthy, lead author of the study and adjunct professor at UNSW Sydney. “A small number of astute venture capitalists have suspected this for some time, but now we have the data to demonstrate this is the case.”

Personality key to start-up success

For the study, the team, which also included researchers from Oxford Internet Institute, the University of Oxford, University of Technology Sydney (UTS), and the University of Melbourne, inferred the personality profiles of the founders of more than 21,000 founder-led companies from language and activity in their publicly available Twitter accounts using a machine learning algorithm. The algorithm could distinguish successful start-up founders with 82.5 per cent accuracy.

They then correlated the personality profiles to data from the largest directory on start-ups in the world, Crunchbase, to determine whether certain founder personalities and their combinations in cofounded teams relate to start-up success – if the company had been acquired, if they acquired another company, or listed on a public stock exchange.

The researchers found that successful start-up founders’ core Big Five personality traits – the widely accepted model of human personality measuring openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism – significantly differ from that of the population at large.

The facets distinguishing successful entrepreneurs include a preference for variety, novelty and starting new things (openness to adventure), like being the centre of attention (lower levels of modesty) and being exuberant (high activity levels).

“The greater presence of these and other personality traits in founders are related to higher chances of success,” says Dr Fabian Braesemann, co-author of the study from the Oxford Internet Institute, University of Oxford.

“We can see how this plays out in many notable examples,” Prof. McCarthy says. “The adventurousness and openness to experience of Melanie Perkins, the assertiveness and confidence of Steve Jobs, the exuberance and energy of Richard Branson, the calm under pressure Jeff Bezos, the discipline and focus of Mark Zuckerberg, and the trustworthiness of Larry Page and Sergey Brin underpin their company’s success.”

Dr. Marian-Andrei Rizoiu, a senior lecturer leading the Behavioural Data Science lab at UTS says: “We used machine learning and a variety of advanced statistical tests to reveal that there is not just one type of successful founder but indeed six types.”

“Our findings clearly show there’s not one ideal ‘founder-type’ personality,” says Associate Professor Margaret (Peggy) Kern, senior author of the study from the University of Melbourne. “Instead, the Big Five personality traits of successful start-up founders, which we can break down further across 30 dimensions, reveal six distinct types: fighters, operators, accomplishers, leaders, engineers and developers.”

While personality is crucial, Prof. McCarthy says many other factors still play a role in the ultimate success of founder-led companies, including luck, timing, and connections.

“Startups, especially during their earliest stages, before there's any demonstrable customer traction rely to a large extent on social proof,” Prof. McCarthy says. “In other words, trust in the founders, which can sometimes present barriers for many groups including women, people who have not worked in tech before, or attended prestigious universities.”

Melanie Perkins, the co-founder of design powerhouse Canva, faced all three of these hurdles in the early days of the company, and was turned down by more than 100 investors before securing the funding they needed to build their product. In an interview, she described herself as “determined, stubborn and adventurous.”[1]

Large, personality-diverse founding teams 

The researchers also undertook multifactor modelling to measure the relative significance of personality on the likelihood of success versus other firm-level variables. They discovered a founder’s personality was more predictive of success than the industry (5 times) and the age of the start-up (2 times).

They also found start-ups with diverse and specific combinations of founder types – an adventurous’ leader’, an imaginative ‘engineer’, and an extroverted ‘developer’, for example – had significantly higher odds of success.

“Firms with three or more founders are more than twice as likely to succeed than solo-founded start-ups,” says Dr Fabian Stephany, co-author of the study from the Oxford Internet Institute, University of Oxford. “Furthermore, those with diverse combinations of types of founders have eight to ten times more chance of success than single founder organisations.”

“While all start-ups are high risk, the risk becomes lower with more founders, particularly if they have distinct personality traits,” Prof. McCarthy says. “Largely founding a start-up is a team sport and now we can see clearly that having complementary personalities in the foundation team has an outsized impact on the venture’s likelihood of success, which we’ve termed the Ensemble Theory of Success.”

The researchers say the findings have critical applications for entrepreneurs, investors, and policymakers and can inform the creation of more resilient start-ups capable of more significant innovation and impact.

“By understanding the impact of founder personalities on start-up success, we can make better decisions about which start-ups to support and help fledgling companies form foundation teams with the best chances of success,” Prof. McCarthy says. 

OpenAI cofounder Sam Altman recognised this when he led the storied start-up accelerator, Y-Combinator, observing in a lecture at Stanford University that “cofounder relationships are among the most important in the entire company.”[2]

The findings also have implications beyond founder-led companies, highlighting the benefits of personality diversity in teams. For example, many fields, such as construction, engineering and the film industry, rely on project-based, cross-functional teams that are often new ventures and share many characteristics of start-ups.

“There are lessons here for organisations of all kinds about the importance of having a diversity of personality types in teams, which can lead to stronger performance and impact,” Prof. McCarthy says.

Just as occupation-personality maps derived from data can provide career guidance tools, information about successful entrepreneurs’ personality traits can also help people decide whether becoming a founder may be a good move for them.

“It’s not part of this study, but we estimate 8 per cent of people worldwide may have personality traits that could make them successful founders,” Prof. McCarthy says. “Likely, many are not in the entrepreneurial field right now.

“Identifying these misfits and people in roles unsuited to their personalities will be the focus of some of our follow-up studies.”

---

[1] https://www.theceomagazine.com/business/coverstory/canva-melanie-perkins/

[2] https://startupclass.samaltman.com/courses/lec02/

---

JOURNAL

Scientific Reports

DOI

10.1038/s41598-023-41980-y 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The impact of founder personalities on startup success

ARTICLE PUBLICATION DATE

17-Oct-2023

 

Familiarity breeds contempt for moral failings

Peer-Reviewed Publication

CORNELL UNIVERSITY

CORNELL UNIVERSITY MEDIA RELATIONS OFFICE

FOR RELEASE: October 17, 2023

Abby Shroba Kozlowski

cell: 607-229-2681

ars454@cornell.edu

Familiarity breeds contempt for moral failings

ITHACA, N.Y. – People judge members of their own circles more harshly than they judge individuals from other groups for the same transgressions, according to new Cornell University research.

Morality plays a central role in this phenomenon. The researchers found that because morality is a social glue that holds a community together, when someone breaks those moral rules inside the group, it is perceived as more of a threat than when outsiders breaks the same rules in their own groups.

“When we’re part of a group, we feel a strong connection to the people in our group, and so we feel they are more likeable or more trustworthy,” said Simone Tang, assistant professor of management and organizations and a co-author of “Morality’s Role in the Black Sheep Effect: When and Why Ingroup Members Are Judged More Harshly Than Outgroup Members for the Same Transgression,” published in the European Journal of Social Psychology.

“However, at the same time, when someone from our group does something morally wrong, it can threaten our social ties and reflect poorly on the whole group, so we judge them harshly to protect the group as a whole,” Tang said.

Tang’s co-authors include Steven Shepherd, associate professor at Oklahoma State University’s Spears School of Business, and Aaron Kay, professor at Duke University’s Fuqua School of Business.

“Ingroup” members may be family or friends and who may share the same political beliefs, hail from the same organization or share the same nationality. In contrast, the “outgroup” may be from a different country or different institution. Contrary to prevalent wisdom that ingroup members always judge other ingroup members more favorably than outgroup members, they found that people made harsher moral judgments against the ingroup transgressor.

Across six studies, 2,361 university students and working American online community members either learned that an ingroup member had behaved badly toward another person in their group, or an outgroup member had done the same thing to another person in the outgroup. For example, students either read that a professor from their own university had been abusive toward other classmates or that a professor from the rival university was abusive toward rival classmates.

The researchers found that moral violations, such as gender discrimination, engendered harsher judgments toward ingroup members than non-moral violations, such as tardiness. This indicated that people cared about an ingroup member’s violation when the social glue of the community – morality – is threatened.

“We hope that our research can help explain real-world puzzles,” Tang said. “In the world of politics, for example, our results provide a different perspective on our current polarized political landscape. Whereas the prevailing thought is that Democrats and Republicans view each other as outgroup members, our research suggests that perhaps the demonization of the other party happens because they view each other as ingroup members (e.g., Americans), hence rendering harsher moral judgments when another ingroup member holds an opposing view. We increasingly see splintering within our groups, and understanding when and why we denigrate and vilify those in our group will be crucial.”

For additional information, see this Cornell Chronicle story.

Cornell University has dedicated television and audio studios available for media interviews.

-30-

---

JOURNAL

European Journal of Social Psychology

DOI

10.1002/ejsp.3001 

 

Cold Spring Harbor Laboratory press announces the release of the medical revolution of messenger RNA by Fabrice Delaye

Includes the story behind the 2023 Nobel Prize in Physiology or Medicine

Book Announcement

COLD SPRING HARBOR LABORATORY PRESS

 

IMAGE: 

RIBOSOME AS PART OF A BIOLOGICAL CELL CONSTRUCTING PROTEIN FROM MESSENGER RNA MOLECULE’S INSTRUCTIONS.

view more 

CREDIT: ENDPAPER STUDIO, GEORGE RESTREPO ISTOCKPHOTO: CHRISTOPH BURGSTEDT

Cold Spring Harbor, NY - Cold Spring Harbor Laboratory Press (CSHL Press), a publisher of scientific books, journals, and electronic media, today announced the publication of The Medical Revolution of Messenger RNA by science and technology journalist Fabrice Delaye.

Many people think it took just ten months to develop a vaccine against the virus that causes COVID-19. What most don’t know is that it was made possible by using messenger RNA (mRNA), the molecule that instructs cells to make a viral protein that stimulates the production of antiviral antibodies, and that this breakthrough technology, which Nobel Prize winner Thomas Cech calls biology’s equivalent of putting a man on the moon, had been in development for three frustrating decades—decades preceded by thirty years of fundamental research. In fact, two scientists, Katalin Karikó and Drew Weissman, won the 2023 Nobel Prize in Physiology or Medicine for their pioneering work in messenger RNA.

Karikó and Weissman are among the many prominent scientists interviewed by veteran science journalist Fabrice Delaye for his book The Medical Revolution of Messenger RNA, which tells the story of how mRNA’s medical potential was finally realized, setting the stage for a coming revolution in which our own bodies will generate the therapeutic molecules we need. Though it’s now thought to show promise for the treatment of everything from cancer to cystic fibrosis to cardiovascular disease, mRNA was long overlooked by mainstream molecular biologists. The path to recognition of its therapeutic possibilities was littered with broken careers, lawsuits, and opportunities missed by pharmaceutical companies. For the scientists who persisted through years of academic and commercial disappointment, the COVID-19 vaccine was a huge vindication and an important step toward a new generation of therapies.

When mRNA-based vaccines came to the rescue during the pandemic in seemingly record time, Delaye realized that their development could not have been as simple and quick as people wanted to believe. But when he tracked down the origins of mRNA technologies, he uncovered a dramatic story that had never been told. Building on decades of contacts and his unique grasp of the science and the stakes involved, Delaye interviewed more than fifty mRNA scientists and entrepreneurs worldwide. His book documents the long, harrowing, unlikely but ultimately triumphant road to a discovery with the potential to revolutionize medicine far beyond the pandemic.

For more information visit https://cshlpress.com/link/messengerrna.htm.

Fabrice Delaye is a science and technology journalist based in Switzerland. He was U.S. correspondent at the daily Swiss newspaper L’Agefi, science and technology editor at magazine Bilan, and is now a reporter-at-large for Heidi.news in Geneva. He is a graduate of the Institut d'Études Politiques de Paris and has a master’s degree from the Swiss Institute of Technology in Lausanne, EPFL.

About Cold Spring Harbor Laboratory Press

Cold Spring Harbor Laboratory Press is an internationally renowned not-for-profit publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. All revenue from sales of CSHL Press publications supports research at Cold Spring Harbor Laboratory.

 

Fungal infection in the brain produces changes like those seen in Alzheimer’s disease

Peer-Reviewed Publication

BAYLOR COLLEGE OF MEDICINE

Previous research has implicated fungi in chronic neurodegenerative conditions such as Alzheimer’s disease, but there is limited understanding of how these common microbes could be involved in the development of these conditions.

Working with animal models, researchers at Baylor College of Medicine and collaborating institutions discovered how the fungus Candida albicans enters the brain, activates two separate mechanisms in brain cells that promote its clearance, and, important for the understanding of Alzheimer’s disease development, generates amyloid beta (Ab)-like peptides, toxic protein fragments from the amyloid precursor protein that are considered to be at the center of the development of Alzheimer’s disease. The study appears in the journal Cell Reports.

“Our lab has years of experience studying fungi, so we embarked on the study of the connection between C. albicans and Alzheimer's disease in animal models,” said corresponding author Dr. David Corry, Fulbright Endowed Chair in Pathology and professor of pathology and immunology and medicine at Baylor. He also is a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. “In 2019, we reported that C. albicans does get into the brain where it produces changes that are very similar to what is seen in Alzheimer’s disease. The current study extends that work to understand the molecular mechanisms.”

“Our first question was, how does C. albicans enter the brain? We found that C. albicans produces enzymes called secreted aspartic proteases (Saps) that breakdown the blood-brain barrier, giving the fungus access to the brain where it causes damage,” said first author Dr. Yifan Wu, postdoctoral scientist in pediatrics working in the Corry lab.

Next, the researchers asked, how is the fungus effectively cleared from the brain? Corry and his colleagues had previously shown that a C. albicans brain infection is fully resolved in otherwise healthy mice after 10 days. In this study, they reported that this occurred thanks to two mechanisms triggered by the fungus in brain cells called microglia.

“The same Saps that the fungus uses to break the blood-brain barrier also break down the amyloid precursor protein into AB-like peptides,” Wu said. “These peptides activate microglial brain cells via a cell surface receptor called Toll-like receptor 4, which keeps the fungi load low in the brain, but does not clear the infection.”

C. albicans also produces a protein called candidalysin that also binds to microglia via a different receptor, CD11b. “Candidalysin-mediated activation of microglia is essential for clearance of Candida in the brain,” Wu said. “If we take away this pathway, fungi are no longer effectively cleared in the brain.”

“This work potentially contributes an important new piece of the puzzle regarding the development of Alzheimer’s disease,” Corry said. “The current explanation for this condition is that it is mostly the result of the accumulation of toxic Ab-like peptides in the brain that leads to neurodegeneration. The dominant thinking is that these peptides are produced endogenously, our own brain proteases break down the amyloid precursor proteins generating the toxic Ab peptides.”

Here, the researchers show that the Ab-like peptides also can be generated from a different source – C. albicans. This common fungus, which has been detected in the brains of people with Alzheimer’s disease and other chronic neurodegenerative disorders, has its own set of proteases that can generate the same Ab-like peptides the brain can generate endogenously.

“We propose that the brain Ab-peptide aggregates that characterize multiple Candida-associated neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease and others, may be generated both intrinsically by the brain and by C. albicans,” Corry said. “These findings in animal models support conducting further studies to evaluate the role of C. albicans in the development of Alzheimer’s disease in people, which can potentially lead to innovative therapeutic strategies.”

For a complete list of the contributors to this work, their affiliations and the financial support for this project, see the publication.

###

---

JOURNAL

Cell Reports

DOI

10.1016/j.celrep.2023.113240 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis

Scientists discover links between Alzheimer’s disease and gut microbiota

Peer-Reviewed Publication

UNIVERSITY COLLEGE CORK

 

IMAGE: 

SCIENTISTS DISCOVER LINKS BETWEEN ALZHEIMER’S DISEASE AND GUT MICROBIOTA. PICTURED ARE DR STEFANIE GRABRUCKER AND PROFESSOR YVONNE NOLAN. IMAGE CREDIT: UCC. 

view more 

CREDIT: IMAGE CREDIT: UCC.

Researchers have discovered the link between the gut microbiota and Alzheimer’s disease.

For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.

The research was led by Professor Yvonne Nolan, APC Microbiome Ireland, a world leading SFI funded research centre based at University College Cork (UCC), and the Department of Anatomy and Neuroscience, UCC, with Professor Sandrine Thuret at King’s College London and Dr Annamaria Cattaneo IRCCS Fatebenefratelli, Italy.

The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer’s disease due to its particular susceptibility to lifestyle and environmental influences.

Published in Brain, the study shows that that the memory impairments in people with Alzheimer’s could be transferred to young animals through transplant of gut microbiota.

Alzheimer’s patients had a higher abundance of inflammation-promoting bacteria in faecal samples, and these changes were directly associated with their cognitive status.

Professor Yvonne Nolan said: “The memory tests we investigated rely on the growth of new nerve cells in the hippocampus region of the brain. We saw that animals with gut bacteria from people with Alzheimer’s produced fewer new nerve cells and had impaired memory.”

“People with Alzheimer’s are typically diagnosed at or after the onset of cognitive symptoms, which may be too late, at least for current therapeutic approaches. Understanding the role of gut microbes during prodromal – or early stage- dementia, before the potential onset of symptoms may open avenues for new therapy development, or even individualised intervention,” said Professor Nolan.

Alzheimer's is the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. As our population ages, one in three people born today are likely to develop Alzheimer’s. Funded by Science Foundation Ireland, scientists in UCC are working to develop strategies to promote healthy brain ageing and advance treatments for Alzheimer’s by exploring how the gut microbiota respond to lifestyle influences like diet and exercise.

Professor Sandrine Thuret, Professor of Neuroscience at King’s College London and one of the study’s senior authors said, “Alzheimer’s is an insidious condition that there is yet no effective treatment for. This study represents an important step forward in our understanding of the disease, confirming that the make-up of our gut microbiota has a causal role in the development of the disease. This collaborative research has laid the groundwork for future research into this area, and my hope is that it will lead to potential advances in therapeutic interventions.”

The research was conducted by Dr Stefanie Grabrucker, a postdoctoral researcher working with Professor Nolan, in partnership with postdoctoral colleagues Dr Edina Silajdzic at King’s College London and Dr Moira Marizzoni, IRCCS Fatebenefratelli, Italy. UCC collaborators were Professor Cora O’Neill, Dr Olivia O’Leary, Dr Sarah Nicolas, Dr Jane English, Mr Sebastian Dohm-Hansen and Dr Aonghus Lavelle.

Professor. John F. Cryan, UCC Vice President for Research and Innovation, who was also involved in this research said: “I’m delighted to be involved in this exciting study that further enhances our understanding of the significant role played by the gut microbiome in brain related diseases, such as Alzheimer’s, and recognises UCC and APC Microbiome Ireland as leading institutions in microbiome and brain health research. This research aligns with our UCC Futures Framework and the strategic plan for the University in the areas of Food, Microbiome and Health and the soon to be launched Future Ageing and Brain Science.”

ENDS

---

JOURNAL

Brain

DOI

10.1093/brain/awad303 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis

ARTICLE PUBLICATION DATE

18-Oct-2023

Western University researchers reveal link between Alzheimer’s and sex hormones

Use of female animal models in the lab led to crucial finding

Peer-Reviewed Publication

UNIVERSITY OF WESTERN ONTARIO

LONDON, ON., CA:

Alzheimer’s disease disproportionately affects women, who represent about two-thirds of those diagnosed with the late-onset type of the disease.

Previous research has shown Alzheimer’s is also more severe and progresses more rapidly in women, and women with Alzheimer’s experience a steeper cognitive decline – loss of memory, attention, and the ability to communicate and make decisions – compared to men with the disease.

The biological bases for these differences between men and women with Alzheimer’s disease are not well understood. However, understanding them is necessary for developing appropriate therapies.

In a new study in mice and humans, Western University researchers have shown female sex hormones play a significant role in how Alzheimer’s manifests in the brain.

The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, also highlights the importance of developing therapeutic strategies focused on these hormonal connections. The research indicates a need to better understand the role of estradiol – a form of the female sex hormone estrogen, used therapeutically to mitigate menopause symptoms – in Alzheimer’s disease.

While the significance of the findings is paramount, the methodology behind them is equally critical, pointing to a necessary shift in scientific approaches.

“To understand how sex hormones play a role in Alzheimer’s, we need to study appropriate animal models. Unfortunately, most studies at this level still focus mainly on the male brain. Our research emphasizes the importance of using animal models that reflect, for instance, postmenopausal women, to understand how sex hormones influence Alzheimer’s pathology,” said Vania Prado, professor, departments of physiology and pharmacology and anatomy & cell biology at Schulich School of Medicine & Dentistry and scientist at Robarts Research Institute. 

This study was led by graduate student Liliana German-Castelan, under the supervision of Vania Prado.

Alzheimer’s and the communication system of the brain

One of the key markers of Alzheimer’s disease is the toxic build-up of the protein beta-amyloid in the brain, which eventually disrupts the brain’s communications system and impacts cognition.

The new study shows that the brain chemistry of male and female mice regulates beta-amyloid protein in Alzheimer’s in different ways, with the hormone estradiol contributing to this variation.

Previous studies on mice and at-risk older individuals have revealed that cholinergic neurons, a type of brain cells that produce the chemical messenger acetylcholine, are particularly vulnerable to the damaging Alzheimer’s-associated beta-amyloid accumulation in the brain. Additionally, acetylcholine has been shown to be essential for normal memory and cognition.

While beta-amyloid aggregation impacts the production of acetylcholine, the subsequent loss of this chemical messenger further increases Alzheimer’s pathology, creating a vicious loop.

The team of Western researchers studied this interaction between changes in brain chemistry and the beta-amyloid protein build-up seen in brains impacted by Alzheimer’s.

“Since male and female brains have differences in the cholinergic system, we wanted to see if sex affects this relationship between acetylcholine signalling and the beta-amyloid protein buildup,” said Marco Prado, professor, departments of physiology and pharmacology and anatomy and cell biology. Marco Prado, one of the authors of the study, is also the Canada Research Chair in Neurochemistry of Dementia and a scientist at Robarts Research Institute.

From bench to real-world: representation of sexes matters

In this study, the researchers observed differences in beta-amyloid accumulation in male and female mice when changing the levels of cholinergic activity. Additionally, they analyzed brain MRI images of healthy older humans.

Different from most studies in humans, in which the MRI scans of man and women are analyzed together, Western professor Taylor Schmitz and graduate student Hayley Shanks analyzed MRI brain scans and the rate of brain loss for aged men and women independently.

“We observed that the relationship between the integrity of the brain region where cholinergic neurons reside and beta-amyloid accumulation was the same for men and women but was different in male and female mice,” said Marco Prado. The researchers suspected that the fact the female mice being studied were not post-menopausal, while women were, could be an attributing factor to the difference.

The lead author of the study, German-Castelan, intrigued by the sex differences, decided to introduce another layer of testing into the mouse models and with the help of Western researcher Robert Gros studied female mice who were closely modelled to represent postmenopausal women. This was done to investigate how the presence or lack of sex hormones could impact the relationship between cholinergic signalling and the beta-amyloid buildup in the brain.

“We found that when the sex hormone estradiol was present, the relationship between acetylcholine and toxic amyloid was lost, but when sex hormones were eliminated in the female mice that relationship reproduced the results seen in humans,” said German-Castelan.

These findings also point to the urgent need to study amyloid and cholinergic function in the ‘peri-menopausal’ age range of 40-50 years, which is much younger than the individuals examined in most large-scale studies of Alzheimer’s disease. Indeed, the sample examined in this study were closer to the age of 70 on average.

“Which explains why there were differences between the results of male and female mice and men and women in our initial exploration,” said German-Castelan.

Researchers emphasized that if they hadn't included female mice in the study, they might have missed crucial information about Alzheimer's and sex differences.

“Women and men respond differently to medications and have a somewhat different journey in Alzheimer’s. To develop more effective therapeutics, we need to study animal models that can reproduce different aspects of the journey. Sex hormones and estradiol levels are just one of these factors,” said Vania Prado. 

Other authors on the study include Western researchers Lisa M. Saksida and Timothy J. Bussey, and Takashi Saito and Takaomi C. Saido of RIKEN Center for Brain Science, Japan

 

 

 

---

JOURNAL

Alzheimer s & Dementia

DOI

10.1002/alz.13481 

ARTICLE TITLE

Sex-dependent cholinergic effects on amyloid pathology: A translational study

ARTICLE PUBLICATION DATE

17-Oct-2023

COI STATEMENT

The authors have no conflicts to disclose.