Cigna, Humana and the Anatomy of (the Coverage of) a Deal – HealthLeaders Media

Update 12/10/23: HumanaDisbandsExecutive Committee, Cigna Disbands Deal

In quantum physics, which governs the smallest bodies, the act of observing an electron changes it. Could this also be true of the Cigna-Humana, two of the healthcare universes largest bodies? Will the act oflooking at the deal by media watchers, financial watchers, and anti-trust watchers change the deal?

Itwould appearyes.

Last Thursday, news broke that Humana, Inc.'s boarded amended its bylaws to remove the requirement for an executive committee, which it then disbanded. But in breaking the potential Cigna-Humana merger on Nov. 29, the WSJ was careful to add assuming the talks dont fall apart. It appears now they have. Cigna has called off the deal due to stockholder pushback and disagreement over financial terms in favor of a now-planned stock buyback and smaller acquisition targets.

Twenty-three daysplus eight years, give or take. Thats how long it took the headlines to change from Cigna explores shedding Medicare Advantage (MA) business to Cigna, Humana in Talks for Blockbuster Merger.

Twenty-three days because news like this travels fast. Eight years because "the current management [of Cigna] has wanted to own HUM for some time (Yahoo! Finance) since 2015, when the two agreed to a merger that the DOJ would ultimately block.

Will that happen again? Answer cloudy, ask again later. But is it worth trying? Apparently yes and for one significant reason: competing with the vertical size and strength of the industrys largest player. [T]he State of U.S. health insurance is UnitedHealthcareall other insurance companies are just trying to keep up with them (Healthcare Huddle).

Heres what we know so far, and what we dont, about how the merger-watching will evolve.

On Nov. 6, a Reuters exclusive announces that Cigna may be looking to sell its 600,000-member Medicare Advantage book of business. Bloomberg now reports that Health Care Service Corporation an independent licensee of the Blue Cross Blue Shield Association is eyeing Cignas MA portfolio.

The reality is Cigna has not captured MA market share and at desired margins like its competitors. Sometimes you have to break something to fix it. Or make it stronger.

Just a week later, STAT asks if a bigger move is being planned, citing a Stephens healthcare stock analysis: We would see this action being one component of a potential pursuit of [Humana] as acquisition target, with the divestiture being a proactive move to reduce antitrust risk.

While the STAT piece was one of the first to ask the question, it took another outlet to answer it . . .

On Nov. 29, The Wall Street Journal announces that a cash-and-stock deal between [the] health-insurance giants could be struck by year-end.

If a deal happens and the merger is approved, the entities will gain from what theyve given. Cigna will have traded some 600,000 MA members for Humanas 5 million. Likewise, Humanas loss of 700,000 commercial lives would be more than offset by Cignas 16 million.

In its pro-merger analysis, Yahoo! Finance quotes Sachin Jain, CEO of SCAN Health Group and Plan, on this trade-off wisdom noting that while it might seem counterintuitive to dump the Medicare business, these are very smart ppl running these companies. [Cigna CEO David]Cordani is a super strategic leader.

Which begs the question . . .

If Cigna and Humana strike a deal, Cigna's larger market cap and revenue ($83B, $181B) compared to Humanas ($62, $93B) would make the latter the likely target. Executive leadership may move in the same direction. Bruce Broussard, Humanas CEO since 2013, is stepping down in later 2024 as part of a multi-year succession plan that reads now like Merger 2.0 . David Cordani has been Cignas President and CEO since 2009.

Since the WSJ story, coverage has concluded that the deal would be:

But its the existing overlap of the two companies PBMs that is being raised most, with STAT noting: Given how Lina Khans Federal Trade Commission already is scrutinizing PBM market power, it seems like that kind of deal would be an insta-block.

Nearly a month since this assessment, not everyone agrees...

In addition to other outlets, HealthLeaders has also covered the merger, the characterization of which has ranged from making sense to making "some sense" (Forbes) to being a really bad idea for Humana (Jim Cramer, CNBC).

The markets observation of a possible deal caused share prices to drop 8% for Cigna, roughly 5.5% the day the WSJ story appeared. After rebounding, Cigna stock dropped another 2% with Humana remaining flat as of Dec. 6.

Market temperature in turn impacts the leadership question. In its follow-up coverage noting the two companies' "limited cost and revenue strategies," Reuters notes: "The limited synergies will also add pressure on Cigna CEO David Cordani to deliver value by running Humana better than its current management."

And what about the government? Optics matter here too. Quoting one analyst on Cigna's proactive MA sale, Reuters adds: "It would be smart to do it even before announcing the deal" (Andre Barlow of Doyle, Barlow and Mazard PLLC).

On the will-it, won't-it be approved question, the WSJ's watchful David Wainer says it best: "A Cigna-Humana merger will be a headache for everyone involved and great business for the lawyers on both sides. But at the end of the day, it is too compelling for either side not to try" (Wall Street Journal).

Laura Beerman is a contributing writer for HealthLeaders.

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Cigna, Humana and the Anatomy of (the Coverage of) a Deal - HealthLeaders Media

Anatomy of a Fall triumphs at the European Film Awards – Cineuropa

11/12/2023 - The film by Justine Triet has dominated proceedings with six wins; other winners include The Promised Land, How to Have Sex, Smoke Sauna Sisterhood and Robot Dreams

Anatomy of a Fall producer David Thion, director Justine Triet and producer Marie-Ange Luciani with their awards ( European Film Academy)

Keeping up the virtually unbroken tradition established in 2016 with the sweeping triumph of Toni Erdmann[+see also: filmreview trailer Q&A: Maren Ade filmprofile], the 36th edition of the European Film Awards, held on 9 December in Berlin, once again witnessed one film stealing the limelight and emerging as the undisputed victor of the night. Interestingly enough, it was another title starring Sandra Hller that dominated the ceremony on this occasion. Anatomy of a Fall[+see also: filmreview trailer interview: Justine Triet filmprofile], the latest Palme d'Or winner by French filmmaker Justine Triet, scooped all of the awards for which it was nominated: European Film, Director, Screenwriter (for Triet and her co-writer Arthur Harari) and Actress (in recognition of Hllers captivating lead performance). In addition to the previously announced Excellence Award for European Editing (see the news) and the European University Film Award, Triet's gripping courtroom drama walked away with a total of six statuettes. This victory also marks the third time in the awards' history that a movie directed by a woman has received the top prize, following the triumphs of Maren Ade in 2016 and Jasmila bani in 2020.

In an unexpected snub, the two films that led the nominations this year, Jonathan Glazer's The Zone of Interest[+see also: filmreview trailer filmprofile] (winner of the Cannes Grand Jury Prize) and Aki Kaurismki's Fallen Leaves[+see also: filmreview trailer filmprofile] (recipient of the Cannes Jury Prize), were left empty-handed in the main categories. While Glazers harrowing portrait of the life of a Nazi official and his family next to the Auschwitz concentration camp received one of the Excellence Awards for European Sound (thanks to the work of Johnnie Burn and Tarn Willers), it ultimately went home without cashing in on any of the five major awards that it had been nominated for. Similarly, Kaurismki's tender romance was completely overlooked in the main categories, along with the migration dramas Green Border[+see also: filmreview trailer filmprofile] and Me Captain[+see also: filmreview trailer filmprofile], directed by Agnieszka Holland and Matteo Garrone, respectively, which premiered at the Venice Film Festival to great acclaim but failed to secure any accolades at the ceremony.

When collecting the coveted Award for European Film, Justine Triet took the opportunity to acknowledge the precious people who are working with me in the shadows, inviting casting director Cynthia Arra and editor Laurent Snchal (recipient of the Excellence Award for European Editing) to join her on stage. She then handed over the microphone to her producer, David Thion, who seized the moment to raise awareness of the impending vote in the European Parliament regarding the proposal to ban geo-blocking technology in Europe. If things change, there is a major threat to cultural diversity in Europe. It could pose a real danger for European sales agents, distributors and producers. [] They are crucial to preserving the way we make films and maintain cultural diversity in Europe, claimed Thion.

The European Film Awards returned to a traditional in-person format in Berlin for the first time since 2019, welcoming over 1,000 international guests. Live-streamed across Europe, the ceremony was hosted by German journalist and actress Britta Steffenhagen, who maintained a light-hearted and humorous tone throughout the gala. However, the event was not without some touching moments and offered a space for reflection on the current state of the world and the arts.

As mentioned above, one of the evening's most celebrated figures was German actress Sandra Hller, who was nominated for not one, but two remarkable performances in The Zone of Interest and Anatomy of a Fall, with the latter earning her Best European Actress. Acting does not happen somewhere in space; it is constantly informed by what is happening in the world at that moment. Yet I'm aware that our thoughts can and will shape the world. [] I would love to be silent with you for a few moments and kindly ask you to strongly, vividly, imagine peace, Hller requested of the audience, who joined her for a minutes silence. Rounding off the acting categories, Danish star Mads Mikkelsen remotely accepted the Best European Actor Award for his captivating turn in the period drama The Promised Land[+see also: filmreview trailer filmprofile] by Nikolaj Arcel, which also received the technical gongs for European Cinematography and Costume Design.

In addition to the Excellence Awards for the different filmmaking crafts, which were revealed a few weeks ago, the other laureates of the 36th European Film Awards included How to Have Sex[+see also: filmreview trailer interview: Molly Manning Walker filmprofile], the directorial debut by British helmer Molly Manning Walker (winner of Un Certain Regard at Cannes this year), which received the European Discovery Prix FIPRESCI, and the Sundance sensation and 2024 LUX Audience Award finalist Smoke Sauna Sisterhood[+see also: filmreview trailer interview: Anna Hints filmprofile] by Anna Hints, who got the audience chanting after claiming the Award for Best European Documentary. Scrapper[+see also: filmreview trailer filmprofile] by the UKs Charlotte Regan earned the European Young Audience Award, while Robot Dreams[+see also: filmreview trailer filmprofile] by Spanish director Pablo Berger was recognised as Best European Animated Feature Film. Finally, Hardly Working by the Austrian collective Total Refusal emerged as the Best European Short Film of the year. As in previous editions, some of these categories were introduced during the ceremony via a series of clips featuring local groups of young people discussing the nominated films.

As previously announced, the European Achievement in World Cinema Award was presented to Spanish director Isabel Coixet. In her acceptance speech, the Barcelona-born filmmaker, boasting a sizeable filmography that includes feature films, series and documentaries produced and shot all over the globe (The Secret Life of Words[+see also: filmreview trailer interview: Isabel Coixet filmprofile], Map of the Sounds of Tokyo[+see also: trailer filmprofile], Endless Night[+see also: filmreview trailer makingof interview: Isabel Coixet filmprofile], The Bookshop[+see also: filmreview trailer filmprofile]), stated: I have made films all around the world because very early in my career, I learned that behind a camera there are no borders, there are no passports, there are no flags and there are no limits. I wish the world could be like this. Coixet's latest work, Un amor[+see also: filmreview trailer interview: Isabel Coixet filmprofile], premiered at the San Sebastin Film Festival and stars Laia Costa (known for her role in Victoria[+see also: filmreview trailer interview: Sebastian Schipper filmprofile]), who had the honour of presenting her with the award at the gala.

Hungarian master Bla Tarr got a standing ovation from the audience as he accepted the Honorary Award of the Academy President and Board. The radical auteur behind masterpieces such as Werckmeister Harmonies, Stntang and The Turin Horse[+see also: filmreview trailer interview: Bla Tarr filmprofile] took a moment to address the newer generation of aspiring filmmakers: They have to find their own language; they have to be themselves; they have to fuck up the film industry But the most important thing is that they have to be free. All of us have to be free. Lastly, the prestigious Lifetime Achievement Award was bestowed upon British actress Vanessa Redgrave. While she was unable to attend the ceremony in person, her presence was felt through a video recorded at her home. In a touching moment, her daughter Joely Richardson handed her the statuette, and both appeared visibly moved. The acknowledgement of Redgrave's distinguished career, which takes in iconic performances such as her role in Michelangelo Antonionis Blow Up, served as a well-deserved tribute to her numerous contributions to the world of cinema.

Here is the full list of winners:

European FilmAnatomy of a Fall[+see also: filmreview trailer interview: Justine Triet filmprofile] - Justine Triet (France)

European Documentary Smoke Sauna Sisterhood[+see also: filmreview trailer interview: Anna Hints filmprofile] - Anna Hints (Estonia/France/Iceland)

European DirectorJustine Triet - Anatomy of a Fall

European ActressSandra Hller - Anatomy of a Fall

European Actor Mads Mikkelsen - The Promised Land[+see also: filmreview trailer filmprofile] (Denmark/Germany/Sweden)

European Screenwriter Justine Triet & Arthur Harari - Anatomy of a Fall

European Discovery Prix FIPRESCI How To Have Sex[+see also: filmreview trailer interview: Molly Manning Walker filmprofile] - Molly Manning Walker (UK/Greece/Belgium)

European Animated Feature FilmRobot Dreams[+see also: filmreview trailer filmprofile] - Pablo Berger (Spain/France)

European Short FilmHardly Working - Total Refusal (Susanna Flock, Robin Klengel, Leonhard Mllner, Michael Stumpf) (Austria)

European Young Audience Award Scrapper[+see also: filmreview trailer filmprofile] - Charlotte Regan (UK)

European Cinematography Rasmus Videbk - The Promised Land

European Editing Laurent Snchal - Anatomy of a Fall

European Production Design Emita Frigato - La Chimera[+see also: filmreview trailer filmprofile] (Italy/Switzerland/France)

European Costume Design Kicki Ilander - The Promised Land

European Make-up & Hair Ana Lpez-Puigcerver, Beln Lpez-Puigcerver, David Mart, Montse Riberker - Society of the Snow[+see also: filmreview trailer interview: JA Bayona filmprofile] (Spain/USA)

European Original Score Markus Binder - Club Zero[+see also: filmreview trailer interview: Jessica Hausner filmprofile] (Austria/UK/Germany/France/Denmark)

European Sound Johnnie Burn & Tarn Willers - The Zone of Interest[+see also: filmreview trailer filmprofile] (UK/Poland/USA)

European Visual Effects Flix Bergs, Laura Pedro - Society of the Snow

European University Film AwardAnatomy of a Fall - Justine Triet

Eurimages Co-Production AwardUljana Kim

European Sustainability Award Prix Film4Climate Gler Sabanc

European Achievement in World Cinema Award Isabel Coixet

Honorary Award of the Academy President and Board Bla Tarr

European Lifetime Achievement Award Vanessa Redgrave

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Anatomy of a Fall triumphs at the European Film Awards - Cineuropa

"Anatomy of a Fall" triumphs at the European Film Awards 2023 – Unifrance Films

The European Film Awards, presented annually since 1988, and which were announced at the ceremony that took place on Saturday, December 9, honored Anatomy of a Fall by Justine Triet, this year's Palme d'or winner, with six awards.

The six awards, corresponding for the first five to all the awards for which the film was nominated, are:

The film also received the European University Film Award, chosen by European students.

For the record, the last time a French film won European Film (majority-French production) at the European Film Awards was in 2012, withc Love de Michael Haneke.

French films also received other awards during the ceremony:

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"Anatomy of a Fall" triumphs at the European Film Awards 2023 - Unifrance Films

‘Lost,’ ‘White Collar’ and ‘This Is Us’ Are Coming to Netflix Thanks to New Deal with Disney – TheWrap

December 11, 2023 @ 1:32 PM

Two major developments are set to take place in the streaming world. The entirety of the Greys Anatomy library will stream on Disneys new one-app experience, and Netflix has secured the streaming rights to 14 beloved library titles from Disney, including Lost, White Collar and ESPNs 30 for 30.

Starting in the spring, Hulu, Disney+ and Netflix will share domestic streaming rights for the ABC medical dramas previous 19 seasons. But those prior seasons will continue to be available to stream on Netflix as part of a new licensing deal betweenthe streamer and Disney, which also includes other shows coming to the competing streamer.

An insider familiar with the arrangement told TheWrap that the deal between Netflix and Disney has not been signed. However, in its current state, it will give the streaming giant licensing access to series such as This Is Us and The Wonder Years.

When the combined Hulu and Disney+ app debuts in late March, follow its beta launch in December, all Greys Anatomy episodes will be made available to stream on both Hulu and Disney+.

New episodes of Greys Anatomy Season 20 will premiere on Hulu the day after their ABC launch, making Hulu the only streamer to carry both the shows full library as well as new in-season episodes.

As for Netflixs new additions, Disney Entertainment has licensed 14 of its non-branded series on a non-exclusive basis. The series are currently licensed to Hulu and other platforms.

Those series include The Wonder Years, This is Us, My Wife & Kids, 25 episodes of ESPNs 30 for 30, The Resident, White Collar, Reba, Archer, How I Met You Mother, Lost, Prison Break, The Hughleys (which is also coming to Hulu), Bernie Mac and Home Improvement. As the titles are added to Netflix, none of the projects will be removed from their existing homes on Hulu, Disney+ or ESPN+.

The deal licensing Disney Entertainment IP to Netflix marks a strategic move for the entertainment giant to expand viewership for certain series, including Prison Break, which aims to promote news of the spin-off series currently in development at Hulu. Given the success on Netflix of USA Network show Suits, the similar member of the channels blue sky era White Collar could find a warm reception in its new location.

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'Lost,' 'White Collar' and 'This Is Us' Are Coming to Netflix Thanks to New Deal with Disney - TheWrap

A look at the curious ‘winter break’ behavior of ChatGPT-4 – ReadWrite

The worlds most popular generative artificial intelligence (AI) is getting lazy as the winter draws in thats the claim from some astute ChatGPT users.

According to a recent ArsTechnica report in late November, users of ChatGPT, the AI chatbot powered by OpenAIs natural language model GPT-4, began noticing something strange. In response to certain requests, GPT-4 was refusing to complete tasks or providing simplified lazy answers instead of the typically detailed responses.

OpenAI acknowledged the issue but claimed they did not intentionally update the model. Some now speculate this laziness may be an unintended consequence of GPT-4 mimicking seasonal human behavior changes.

Dubbed the winter break hypothesis, the theory suggests that because GPT-4 is fed the current date, it has learned from its vast training data that people tend to wrap up big projects and slow down in December. Researchers are urgently investigating whether this seemingly absurd idea holds weight. The fact its being taken seriously underscores the unpredictable and human-like nature of large language models (LLMs) like GPT-4.

On November 24th, a Reddit user reported asking GPT-4 to populate a large CSV file, but it only provided one entry as a template. On December 1st, OpenAIs Will Depue confirmed awareness of laziness issues related to over-refusals and committed to fixing them.

Some argue GPT-4 was always sporadically lazy, and recent observations are merely confirmation bias. However, the timing of users noticing more refusals after the November 11th update to GPT-4 Turbo is interesting if coincidental and some assumed it was a new method for OpenAI to save on computing.

On December 9, developer Rob Lynch found GPT-4 generated 4,086 characters when given a December date prompt versus 4,298 for a May date. Although AI researcher Ian Arawjo couldnt reproduce Lynchs results to a statistically significant degree, the subjective nature of sampling bias with LLMs makes reproducibility notoriously difficult. As researchers rush to investigate, the theory continues intriguing the AI community.

Geoffrey Litt of Anthropic, Claudes creator, called it the funniest theory ever, yet admitted its challenging to rule out given all the weird ways LLMs react to human-style prompting and encouragement, as shown by the increasingly weird prompts. For example, research shows GPT models produce improved math scores when told to take a deep breath, while the promise of a tip lengthens completions. The lack of transparency around potential changes to GPT-4 makes even unlikely theories worth exploring.

This episode demonstrates the unpredictability of large language models and the new methodologies required to understand their ever-emergent capabilities and limitations. It also shows the global collaboration underway to urgently assess AI advances that impact society. Finally, its a reminder that todays LLMs still require extensive supervision and testing before being responsibly deployed in real-world applications.

The winter break hypothesis behind GPT-4s apparent seasonal laziness may prove false or offer new insights that improve future iterations. Either way, this curious case exemplifies the strangely anthropomorphic nature of AI systems and the priority of understanding risks alongside pursuing rapid innovations.

Featured Image: Pexels

Radek Zielinski is an experienced technology and financial journalist with a passion for cybersecurity and futurology.

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A look at the curious 'winter break' behavior of ChatGPT-4 - ReadWrite

Neuroscience and Behavior Major (B.S.) | College of Liberal Arts – UNH’s College of Liberal Arts

The major in neuroscience and behavior (NSB) offers an interdisciplinary approach to human and non-human behavior, focusing on the evolution and adaptiveness of certain behaviors, as well as their underlying neural mechanisms. Students who have always been fascinated by how the brain functions will be well served by this major, as will those who love wild animals and wish to better understand their behavior. The B.S. in neuroscience and behavior is based on a solid foundation in biology, chemistry, physics, statistics, and genetics (foundation courses). These are followed by a two-semester course sequence that covers the fundamentals of neuroscience and behavior. Students can then pick five or more electives focusing on areas of interest.

NSB students are encouraged to take advantage of research experiences in the laboratories of the psychology and biology faculty in the program. This provides valuable experience with cutting-edge equipment and techniques. Some students may share aspects of a larger project, whereas others may be relatively independent and design their own project under supervision. In either case, important skills are gained by the discipline of gathering data, analyzing and interpreting it, and presenting it to a broader audience.

The curriculum provides most of the requirements and recommended courses for students seeking admission to graduate school and to professional schools in medicine and veterinary medicine. Students who might choose not to go on to advanced degrees are well-prepared for employment as skilled technicians in research laboratories or, if their interests are in animal behavior, as field research assistants or animal trainers. With additional courses in education, the B.S. in NSB also qualifies graduates to teach at the elementary, junior high, and high school levels.

Faculty participating in the NSB major combine a love of teaching and student mentoring with a passion for research, and encourage student participation. Research facilities that students can use include the Integrative Animal Behavior and Ecoacoustics laboratory, the confocal imaging center, the Hubbard Center for Genomic Studies, and the many marine, freshwater, and estuarine laboratories associated with UNH programs. Students can also take summer courses at the Shoals Marine Laboratory.

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Neuroscience and Behavior Major (B.S.) | College of Liberal Arts - UNH's College of Liberal Arts

Clues to preventing Alzheimer’s come from patient who, despite genetics, evaded disease Washington University … – Washington University School of…

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Breaking link between early, late stages of disease may prevent dementia

A woman who never developed Alzheimer's despite a strong genetic predisposition may hold the key to stopping the disease in its tracks. Studying the woman's unique complement of genetic mutations, researchers at Washington University School of Medicine in St. Louis have found clues that could help cut the link between the early, asymptomatic stage and the late stage, when cognitive decline sets in.

Alzheimers disease has plagued one large Colombian family for generations, striking down half of its members in the prime of life. But one member of that family evaded what had seemed would be fate: Despite inheriting the genetic defect that caused her relatives to develop dementia in their 40s, she stayed cognitively healthy into her 70s.

Researchers at Washington University School of Medicine in St. Louis now think they know why. A previous study had reported that, unlike her relatives, the woman carried two copies of a rare variant of the APOE gene known as the Christchurch mutation. In this study, researchers used genetically modified mice to show that the Christchurch mutation severs the link between the early phase of Alzheimers disease, when a protein called amyloid beta builds up in the brain, and the late phase, when another protein called tau accumulates and cognitive decline sets in. So the woman stayed mentally sharp for decades, even as her brain filled with massive amounts of amyloid. The findings, published Dec. 11 in the journal Cell, suggest a new approach to preventing Alzheimers dementia.

Any protective factor is very interesting, because it gives us new clues to how the disease works, said senior author David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. As people get older, many begin to develop some amyloid accumulation in their brains. Initially, they remain cognitively normal. However, after many years the amyloid deposition begins to lead to the accumulation of the tau protein. When this happens, cognitive impairment soon ensues. If we can find a way to mimic the effects of the APOE Christchurch mutation, we may be able to stop people who already are on the path to Alzheimers dementia from continuing down that path.

Alzheimers develops over the course of about 30 years. The first two decades or so are silent; amyloid slowly accumulates in the brain without causing ill effects. When amyloid levels reach a tipping point, however, they kick off phase two, which involves multiple interrelated destructive processes: A protein called tau forms tangles that spread through the brain; brain metabolism slows down, and the brain begins to shrink; and people start to experience memory and thinking problems. The disease follows the same pattern in people with genetic and nongenetic forms of Alzheimers.

The Colombian families carry a mutation in a gene called presenilin-1 that causes their brains to develop far too much amyloid buildup beginning in their 20s. People who carry the mutation accumulate amyloid so quickly that they reach the tipping point and start showing signs of cognitive decline in middle age. One rare exception is a woman who had more amyloid in her brain in her 70s than her relatives did in their 40s, but only very minimal signs of brain injury and cognitive impairment.

One of the biggest unanswered questions in the Alzheimers field is why amyloid accumulation leads to tau pathology, Holtzman said. This woman was very, very unusual in that she had amyloid pathology but not much tau pathology and only very mild cognitive symptoms that came on late. This suggested to us that she might hold clues to this link between amyloid and tau.

A 2019 study had revealed that, along with a mutation in presenilin-1, the woman also carried the Christchurch mutation in both copies of her APOE gene, another gene associated with Alzheimers disease. But with only one person in the world known to have this particular combination of genetic mutations, there were not enough data to prove that the Christchurch mutation was responsible for her remarkable resistance to Alzheimers and not simply a coincidental finding.

To solve this puzzle, Holtzman and first author Yun Chen, a graduate student, turned to genetically modified mice. They took mice genetically predisposed to overproduce amyloid and modified them to carry the human APOE gene with the Christchurch mutation. Then, they injected a tiny bit of human tau into the mouse brains. Normally, introducing tau into brains already brimming with amyloid seeds a pathological process in which tau collects into aggregates at the site of injection, followed by the spread of such aggregates to other parts of the brain.

Not so in the mice with the Christchurch mutation. Much like the Colombian woman, the mice developed minor tau pathology despite extensive amyloid plaques. The researchers discovered that the key difference was the activity levels of microglia, the brains waste-disposal cells. Microglia tend to cluster around amyloid plaques. In mice with the APOE Christchurch mutation, the microglia surrounding amyloid plaques were revved up and hyperefficient at consuming and disposing of tau aggregates.

These microglia are taking up the tau and degrading it before tau pathology can spread effectively to the next cell, Holtzman said. That blocked much of the downstream process; without tau pathology, you dont get neurodegeneration, atrophy and cognitive problems. If we can mimic the effect that the mutation is having, we may be able to render amyloid accumulation harmless, or at least much less harmful, and protect people from developing cognitive impairments.

Chen Y, Song S, Parhizkar S, Lord J, Zhu Y, Strickland MR, Wang C, Park J, Tabor GT, Jiang H, Li K, Davis AA, Yuede CM, Colonna M, Ulrich JD, Holtzman DM. APOE3ch alters microglial response and suppresses A-induced tau seeding and spread. Cell. Dec. 11, 2023. DOI: 10.1016/j.cell.2023.11.029

This study was supported by the JPB Foundation; Cure Alzheimers Fund; the National Institutes of Health (NIH), grant numbers RF1AG047644 and RF1NS090934; and the Alzheimers Association, grant number AARF-21-850865. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Holtzman is an inventor on a patent licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies; co-founded and is on the scientific advisory board of C2N Diagnostics; is on the scientific advisory board of Denali, Genentech, and Cajal Neuroscience; consults for Asteroid; and is on the Advisory Board for Cell. Colonna is a member of the Vigil Neuro scientific advisory board and is a consultant for Cell Signaling Technology and NGM Bio. The rest of the authors have no conflict of interests.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Childrens hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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Clues to preventing Alzheimer's come from patient who, despite genetics, evaded disease Washington University ... - Washington University School of...

Intermountain Health study offering free genetic testing will end this month – KSL.com

Estimated read time: 3-4 minutes

SALT LAKE CITY Intermountain Health will be pausing enrollment in the HerediGene: Population Study, which provides people an opportunity to participate in genetic research.

"We have been incredibly appreciative of the community support and willingness to participate in the HerediGene: Population Study. The genetic discoveries from this study have been monumental," Brad Gillman, an Intermountain spokesman, told KSL.com.

"Because of these efforts, we have reached a point where we will be pausing the enrollment of this study as of Dec. 28. This will allow us to focus on returning results to the participants and generating more discoveries," he said.

Until then, people interested in enrolling can sign up online, or simply go to any Intermountain lab and say they want to participate in the research. Less than 2.5 teaspoons of blood is necessary for sequencing, Intermountain Health's website says.

The study is the largest DNA study in the United States, and has been ongoing since mid-2019. It aims to improve health care intervention for anyone at risk of serious diseases, and to help prevent chronic illnesses like diabetes, heart disease and cancer. All U.S. residents 18 and older are eligible for participation.

HerediGene has already changed the lives of many Utahns.

Former KSL-TV reporter Keith McCord discovered through the study he has genetic markers for hereditary hemochromatosis, which can be managed with treatment but may have irreversible health implications if left untreated. He discovered his diagnosis before any symptoms arose.

Three generations of Elissa Smith's family got the free risk assessment after her father survived colon cancer.

The study informed Madison Certonio she has the BRCA2 gene, which causes women to have between a 45% and 85% chance of developing breast cancer in their lives, and men to have between a 20% and 50% chance of developing prostate cancer.

"It's been a little stressful. It's been a little emotional," she said in an promotional video produced by Intermountain. "But then you have to be happy because you know (the risk). Since I'm 25 and I know, I can get all the screenings done to prevent it, because knowledge is power."

Participants who do not bear any genetic markers will not be contacted by Intermountain; but if markers are discovered, they will be contacted by phone or letter to schedule an appointment with a genetic counselor should they wish to find out what the gene is.

A large sequencing sample regardless of whether an individual participant has a harmful gene is useful to doctors and scientists in discovering new genetic risk factors and treating existing patients.

"We anticipate spin-off studies that will target the genetics of specific diseases will occur over the next several years," Gillman said. "Intermountain Health continues to be committed to precision medicine to help our patients, and their families, live the healthiest lives possible."

Correction: The HerediGene study does not provide free genetic testing for any condition, as a previous version might have indicated. It involves research on specific genes, to better predict and prevent serious disease.

Katie Workman is a former KSL.com and KSL-TV reporter who works as a politics contributor. She has degrees from Cambridge and the University of Utah, and she's passionate about sharing stories about elections, the environment and southern Utah.

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Intermountain Health study offering free genetic testing will end this month - KSL.com