Category: News & events

Symposium highlights studies from brain to heart

Researchers from MIT and beyond shared research they are doing to help people with Down syndrome
A cartoon of a brain shows different regions (visual cortex, audio cortex, prefrontal cortex and hippocampus) lit in different colors. Next to the brain is a chart of brainwaves in each region. In the upper right of the image there is an inset of Roberta Fonseca speaking.

Research progress has helped people with Down syndrome enjoy longer lives, but scientists recognize they can still do much more to ensure that those longer lifespans are more healthful. An April 9 online symposium of the Alana Down Syndrome Center at MIT highlighted seven projects across three universities aiming to do exactly that.

“Today, if you’re born with Down syndrome, you can expect to live 60 or more years. There are people with Down syndrome that have lived well into their 80s,” said Rosalind Firenze, scientific director of the Alana Center based in The Picower Institute for Learning and Memory at MIT. “But unfortunately, when we think about the health of people with Down syndrome, research into medicine and health has been historically underfunded, and often people with Down syndrome are excluded from research.

“So there are many unknown things about Down syndrome biology and neuroscience, but it’s really important to search for answers, because what we do know is that our loved ones with Down syndrome have a heightened risk for a number of conditions,” Firenze added.

Mindful of these disparities, Picower Professor Li-Huei Tsai and colleagues founded the Alana Down Syndrome Center (ADSC) at MIT in 2019 with the generous support of the Alana Foundation. Its mission, Firenze said, is to “build research, training and technology for a world of greater inclusion, possibility and accessibility for people with Down syndrome.”

In the symposium “Accelerating Research for Down Syndrome,” three ADSC supported fellows presented their projects on brain and heart development alongside four researchers from Rutgers University and the University of São Paolo (USP) in Brazil, who discussed their studies of cognition and brain health over the lifespan.

Brains young to old

In 2024, Tsai’s Picower Institute lab showed that in mice exposed to light flickering and sound clicking at the 40Hz frequency of gamma brain waves, specific neurons increased their output of the peptide VIP. Other studies indicate the peptide has important roles in fetal brain development. In her symposium talk, Alana Fellow and postdoc Roberta Fonseca described how members of the lab have begun testing whether exposure to the sensory stimulation among pregnant mice increases VIP in the womb and benefits brain development of their fetuses in a model of Down syndrome. They are also testing whether applying VIP to developing human stem cell cultures with trisomy 21 enhances their survival and metabolic health. The lab is still working on the experiments, including memory tests for Down syndrome mice born from mothers that were exposed to the 40Hz stimulation, compared to unstimulated controls.

USP Professor Daniele De Paula Faria presented her work on brain imaging of both people with Down syndrome and mouse models at ages old and young. She’s using positron emission tomography (PET) scanning to track key molecular indicators of metabolism and inflammation. In a study she published last year in Alzheimer’s & Dementia, for instance, she and colleagues showed that people with Down syndrome show significantly greater neuroinflammation compared with neurotypical people as young as age 20 and that the increased inflammation correlates strongly with amyloid plaque, which are well-known biomarkers of Alzheimer’s disease. She has seen similar indications in mice and has begun testing potential interventions.

Also looking across the lifespan for predictors of Alzheimer’s development, Rutgers Assistant Professor Luciana Fonseca described her work studying how cognitive variability at a single point within individuals with Down syndrome can provide important information about AD risk and resilience. Rather than capturing sparse snapshots of cognition, as many clinicians do, she is leading a study in which her team assesses cognitive performance across tasks and tests to enable measurements of variability. Her hypothesis is that the greater the degree of variability, the higher the risk of developing dementia. In the study she’s also collecting other potential biomarkers associated with Alzheimer’s onset.

Rutgers graduate student Chuhanwen Sun, meanwhile, presented his research aimed at understanding at the cellular level what makes the brain vulnerable to Alzheimer’s disease in Down syndrome. Using postmortem brain samples from Down syndrome individuals who did or did not develop Alzheimer’s, he has engaged in a deep analysis of gene expression and epigenetic differences in individual cell types. The work is still ongoing but he said the research is pinpointing specific cells in a specific brain region as being especially vulnerable.

Since 2019, USP Professor Orestes Forlenza, a geriatric psychiatrist, has been enrolling hundreds of adults with Down syndrome in a study aimed at better understanding how various blood-based biomarkers track with changes in cognition over the lifespan. Among these are markers of cellular oxidative stress, measures of cell death or “apoptosis,” and a form of molecular signaling called the wnt pathway. He’s also been able to rule out other suspected biomarkers that don’t correlate with cognitive impairment in Down syndrome volunteers.

The developing heart

Two postdocs supported by the ADSC and working in the lab of MIT Biology Professor and ADSC investigator Laurie Boyer talked about their research on the heart. Their goal is to identify factors at play in the earliest stages of development to better understand, and potentially intervene to prevent, congenital heart defects that are much more common in people with Down syndrome than in the general population.

Alana Fellow Mehdi Hamouda investigates how physical forces on developing heart cells may differ in trisomy 21 vs. in cells that have the typical two chromosome copies. The forces on cells can impact the nucleus, affecting how stem cells ultimately become more specific cells in the body, including the cardiomyocytes that build the heart. His hypothesis is that trisomy 21 causes faulty mechanical cues that change how the nucleus feels and responds to these forces to impact the earliest stages of heart development.

Meanwhile, NRSA postdoc Leah Borden presented her work integrating both mouse hearts from Down Syndrome models and trisomy 21 cells from individuals with DS. Her research investigates how developing heart cells engage with their surrounding environment, the “extracellular matrix” (ECM), to regulate critical tissue properties that guide differentiation. Leah is uncovering how Trisomy 21-associated alterations in ECM reshapes the mechanical and signaling landscape during heart development.

In all, the symposium provided seven examples of how ADSC researchers and their colleagues are racing to better understand factors that affect the lifelong health of people with Down syndrome.

Accelerating Research for Down Syndrome

Join our webinar on April 9th 2026, 11-1 (ET)
EventsApril 9, 2026
An electron microscopy image of cells and extracelluar matrix.

Join us for our 2026 webinar: Accelerating Research for Down Syndrome to be held April 9th 2026, 11-1 PM (EST); 12-2 PM (Brazil), via Zoom.

In this webinar, a diverse set of researchers from MIT, University of São Paulo and Rutgers University will present short talks on their research on Down syndrome and related conditions, such as Alzheimer’s disease and congenital heart defects, as well as new technologies that accelerate research progress. The audience will have a chance to ask the scientists about their work at the end of each talk.

REGISTER

Speakers 

Rosalind Firenze, Scientific Program Director The Alana Down Syndrome Center at MIT

Leah Borden, NRSA Postdoctoral Fellow Boyer Lab, MIT

Mehdi Hamouda, Alana Fellow Boyer Lab, MIT

Roberta Fonseca, Alana Fellow Tsai Lab, MIT

Daniele de Paula Faria, Associate Professor University of São Paulo

Chuhanwen (Silas) Sun, Graduate Student Yang Lab, Rutgers University

Luciana Mascarenhas Fonseca, Assistant Professor Rutgers University

Orestes Forlenza, Professor University of São Paulo

 

Organizers

Rosalind Firenze, The Alana Down Syndrome Center at MIT
Orestes Forlenza, University of São Paulo
Brittany Greenough, The Picower Institute of Learning and Memory

Host

Li-Huei Tsai, Director, The Alana Down Syndrome Center at MIT

2025 Spring Webinar Recap

Learn more about our webinar, co-sponsored by the Massachusetts Down Syndrome Congress
Screenshot of the webinar presentation featuring the Alana Down Syndrome Center

This past April, an Alana Down Syndrome Center webinar, co-sponsored by the Massachusetts Down Syndrome Congress, presented numerous MIT studies that all share the goal of improving health throughout life for people with trisomy 21.

In recent decades the life expectancy of people with Down syndrome has surged past 60 years, so the focus of research at the Alana Down Syndrome Center at MIT has been to make sure people can enjoy the best health during that increasing timeframe.

“A person with Down syndrome can live a long and happy life,” said Rosalind Mott Firenze, scientific director of the center founded at MIT in 2019 with a gift from the Alana Foundation. “So the question is now how do we improve health and maximize ability through the years? It’s no longer about lifespan, but about healthspan.”

Firenze and three of the center’s Alana Fellows scientists spoke during a webinar, hosted on April 17th, where they described the center’s work toward that goal. An audience of 99 people signed up to hear the webinar titled “Building a Better Tomorrow for Down Syndrome Through Research and Technology,” with many viewers hailing from the Massachusetts Down Syndrome Congress, which co-sponsored the event.

Watch the webinar here.

Read more about the webinar here.

In a mouse model of Down syndrome, 40Hz light and sound improve cognition, neurogenesis, connectivity

Study provides evidence that sensory stimulation of gamma brain rhythms may promote restorative neurological health response.
ResearchApril 25, 2025
Research Paper
image of brain sections stained for the formation of new neurons

Studies by a growing number of labs have identified neurological health benefits from exposing human volunteers or animal models to light, sound and/or tactile stimulation at the brain’s “gamma” frequency rhythm of 40Hz. In the latest such research at The Picower Institute for Learning and Memory and Alana Down Syndrome Center at MIT, scientists found that 40Hz sensory stimulation improved cognition and circuit connectivity and encouraged the growth of new neurons in mice genetically engineered to model Down syndrome.

Li-Huei Tsai, Picower Professor at MIT and senior author of the new study in PLOS ONE, said that the results are encouraging but also cautioned that much more work is needed to test whether the method, called GENUS (for Gamma Entrainment Using Sensory Stimulation), could provide clinical benefits for people with Down syndrome.

Story continues…

 

Alana Down Syndrome Center at the 2024 World Down Syndrome Congress

The power of inclusive research
EventsIdeas & PerspectivesJuly 31, 2024
Panelist Jaspreet Kaur Sekhon shakes hands with the host, Professor Rhonda Faragher at the World Down Syndrome Congress.
Jaspreet Kaur Sekhon and Professor Rhonda Faragher at a plenary session featuring ADSC

In Brisbane, Australia, the World Down Syndrome Congress convened in-person for the first time since 2018. Over 1000 delegates from 45 countries met from July 9th – 12th, 2024, for the central theme of “Together We Can: Celebrating Diversity and Inclusion.” The event allowed families, advocates and professionals from the global Down syndrome community to gather and discuss all aspects of health, research, education, employment, inclusion and personal development. The Alana Down Syndrome Center (ADSC) of MIT was honored to be featured in a plenary session focused on the center’s ongoing research supported by the Alana Foundation.

The session, chaired by Professor Rhonda Faragher, was not a typical scientific meeting, as it included self-advocates and families as participants in the discussion. Panelists included Jaspreet Kaur Sekhon from Singapore who has overcome adversity as a leading self-advocate for Down syndrome. Her long list of accolades includes a keynote presentation at the United Nations, and decades of dance performance and instruction for young people with disabilities. Jessamy Tang, MIT graduate and Managing Director of the Stanford Down Syndrome Research Center, and Nathan Rowe, Program Director at Down Syndrome International, rounded out the panel with their deep expertise in disability inclusion.

An image of the panel members, host and speaker seated at the discussion table on stage.
The plenary session panel (left to right): Jessamy Tang, Jaspreet Kaur Sekhon, Nathan Rowe, Rhonda Faragher, Rosalind Firenze.

 

The program director of ADSC, Dr. Rosalind Firenze, featured the work of the center and highlighted the recent clinical study, led by Dr. Diane Chan and Picower Professor Li-Huei Tsai, Director of the ADSC and The Picower Institute for Learning and Memory of MIT. Tsai’s group is developing a ground-breaking, non-invasive therapy for Alzheimer’s disease known as ‘GENUS’ – gamma entrainment through non-invasive 40Hz sensory stimulation. The landmark clinical trial, the first to study the effects of GENUS in people with Down syndrome, was recently completed at MIT. The results are currently being analyzed with initial outcomes indicating that light and sound stimulation can increase the strength of 40Hz gamma rhythms in the brain and may provide cognitive benefits in the short-term. Long-term studies in people with Down syndrome and Alzheimer’s disease are still needed to test the therapeutic efficacy of this non-invasive approach.

 

Firenze also highlighted another MIT invention: ZzAlign, which is a comfortable, mouth-piece device under development to help people with obstructive sleep apnea (OSA) keep airways open. The new device incorporates digital intraoral scans, 3D printing technology and an innovative smart-pump design to apply a gentle suction pressure to hold the tongue in place, effectively opening airways during sleep. OSA impacts the majority of adults with Down syndrome and impacts their overall health. The development of ZzAlign is led by Professor Ellen Roche‘s lab and the Deshpande Center for Technological Innovation. The team is currently entering clinical trials to test the device’s efficacy during sleep in people with OSA.

 

Families and self-advocates learned about other ADSC research, including the use of iPSC (induced pluripotent stem cell) models to study changes in heart development and application of GENUS to improve neurodevelopment in the T65Dn mouse model of Down syndrome.  After learning about the research tools and progress, audience members participated in an engaging discussion on the role of scientific research in attaining a higher quality of life for people with Down syndrome. Sekhon pointed out the importance of including self-advocates in research design and discussions to ensure that their needs are considered and incorporated. Tang further championed the concept of consulting with families in the early stages of clinical trial design to ensure that participation is accessible and comfortable. Rowe also pointed out that once technologies and therapies are developed it is important to make them available in a fair and equitable way. Audience members asked questions about how the model systems relate back to people with Down syndrome and when therapies like GENUS might become available.

By connecting the Down syndrome community directly to cutting-edge research at MIT, the plenary session felt momentous with an important take-away: inclusivity can push science further. Jaspreet Kaur Sekhon said it best herself, as she thanked researchers at ADSC and the panel, “You all were very inclusive, in giving me this Voice and listening to me.”

Symposium examines intersecting biology of neurodegeneration, Down syndrome

Cross-cutting examples of disease pathology, cellular breakdowns highlight joint conference
EventsOctober 11, 2022

Talk Videos

Watch videos of several of the symposium talks on YouTube.

Neuroscientists still have a tremendous amount to learn about the causes and courses of neurodegenerative diseases and Down syndrome, but as speakers at the Oct. 5-6 MIT symposium “Glial and Neuronal Biology of the Aging Brain” pointed out, often when they make a new discovery in the context of one such condition, it teaches them something relevant to others.

“Our belief is that the study of the aging brain can learn a great deal from the study of Down syndrome and vice versa,” said Picower Professor Li-Huei Tsai who directs the two MIT entities that jointly hosted the conference: The Aging Brain Initiative and the Alana Down Syndrome Center. “It would be a wonderful outcome of this symposium if we can play even a small role in bringing these two communities of scientists, physicians, and engineers, and even caregivers closer together.”

The event indeed marshaled a multitude of online attendees. Over the course of the two-day program more than 400 people tuned in from 27 countries. They heard scientists from places as far-ranging as Hong Kong and Germany share their latest research and discuss the many intersections they see among Alzheimer’s and other dementias, Parkinson’s disease, Huntington’s disease and Down syndrome.

For example, Tracy Young Pearse, associate professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, discussed her lab’s new finding that the three copies of the genes APP and DYRK1A found in Down syndrome neurons (because they have three copies of chromosome 21), increase phosphorylated tau (a pathological hallmark of Alzheimer’s) and promote excessive transport and release of neurotransmitters across connections with other neurons, a potential source of circuit dysfunction.

Vessels of concern

Though neural circuits remain at the heart of brain function, three speakers instead focused their talks on the brain’s circulatory system. MIT Associate Professor Myriam Heiman noted that the breakdown of the blood-brain barrier, which strictly filters what the body and brain exchange, are suspected of being key contributor to many neurodegenerative diseases. In presenting her lab’s new research that produced a novel “atlas” of cell types in the brain’s blood vessels, she showed clear evidence that vascular integrity is weakened in Huntington’s disease and that the degradation is associated with a problematic innate immune response.

Elizabeth Head, Professor of pathology and laboratory medicine at the University of California at Irvine, related dysfunction of brain vasculature to the connection between Down syndrome and Alzheimer’s. Though people with Down syndrome are relatively protected against cardiovascular problems such as high blood pressure or atheroma, an excess of amyloid protein in their brain blood vessels leads to cerebral amyloid angiopathy, a condition closely associated with Alzheimer’s. Head’s lab has shown that people with Down syndrome and CAA exhibit microbleeds along their brain blood vessels.

Head collaborates with Adam Brickman, professor of neuropsychology at Columbia University. He presented recent studies showing that magnetic resonance imaging of “white matter hyperintensities” and other vascular problems can be a biomarker of Alzheimer’s pathology in people with Down syndrome. The hyperintensities, which the team showed to be especially prevalent in posterior lobes of the brain, are believed to be the result of brain vasculature problems and correlated with other problems such as microbleeds.

Symposium speaker Adam Brickman and moderator and former Alana Fellow Jackie Yang

Cells not immune from scrutiny

Several other speakers focused on the brain’s immune cells, called microglia, which have a very complex role in neurodegenerative diseases including Alzheimer’s.

Microglia, for instance, take on many different states in Alzheimer’s ranging from beneficial to harmful. In her talk, Harvard Medical School & Boston Children’s Hospital neurology Associate Professor Beth Stevens described methods her lab has developed for culturing microglia from stem cells and then coaxing them into these many states by tailoring either their genetic background, their environmental context, or both.

Li Gan, professor of neuroscience at Weill Cornell Medicine, discussed particular instances in which molecularly manipulating microglial state can sustain the brain’s resilience to Alzheimer’s pathology. In a study published earlier this year her lab found that by reducing expression of the gene transcription factor NFkappaB in microglia, the lab could reduce spreading of the problematic protein tau. She also shared even newer results showing that intervening in a specific runaway immune pathway in microglia by knocking down a key molecule, her lab has shown benefits in learning and memory in mice. The method appears to do so by increasing activity of a resilience-promoting transcription factor called MEF2 that Tsai’s lab has also independently identified as beneficial.

Hong Kong University of Science and Technology Professor Nancy Yuk-Yu Ip detailed another molecular method of helping microglia combat Alzheimer’s. Her lab has found that in the disease a soluble form of the molecule ST2 intercepts the immune molecule interleukin 33 (IL-33), which would normally prompt a transition of microglia into a beneficial state. The lab has shown that injecting IL-33 improves Alzheimer’s pathology in mice and has found a genetic variant in people that conveys protection against this problem.

Three images are stacked in the frame. Across the top are head and shoulders pictures of Michael Heneka on the left and Ravi Raju on the right. They are listening as Li-Huei Tsai (on the bottom) speaks.
MIT Professor Li-Huei Tsai asks a question while speaker Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine, and moderator Ravi Raju, an MIT postdoc, listen.

In his talk, Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine, showed how microglia literally throw neurons a line to help them fight back against toxic proteins. His lab found that microglia extend “tunneling nanotubes” to neurons beset with tau (a toxic aggregate in some dementias) or alpha-synuclein (a toxic aggregate most prevalent in Parkinson’s disease) to remove the proteins and to supply neurons with fresh mitochondria to rescue them from oxidative stress.

A system with many parts

Neurons, vascular cells, and microglia were not the only cells with time in the spotlight. Shane Liddelow, assistant professor of neuroscience and physiology at New York University focused on astrocytes, an abundant cell type in the brain with key roles in supporting neural function and linking neurons to blood vessels. He shared new research indicating that subtypes of astrocytes have inflammatory responses in disease and in the case of Alzheimer’s, associate with pathology in particular parts of the brain. Further research can help determine what those subtypes may matter to the progression of the disease.

Astrocytes, neurons and microglia were all featured in the remarks of Gilbert Di Paolo, executive director of discovery biology at Denali Therapeutics. He discussed the company’s potential therapy for a subset of cases of frontotemporal dementia. In those cases, mutations reduce levels of progranulin, which undermines the function of cells’ lysosomes. By restoring levels of progranulin in cells the company is restoring lysosomal function and therefore indicators of cell health.

Complementing the talks’ exposition of the variety of cell types and molecular mechanisms at issue across neurodegenerative diseases and Down syndrome were the posters of MIT postdocs and graduate students that followed the talks. A dozen presenters from seven labs affiliated with the Aging Brain Initiative, the Alana Center, or both highlighted whole systems approaches to understanding and treating disease. Members of Tsai’s lab, for instance, discussed the therapeutic possibilities for Down syndrome of stimulating the brain with light and sound at the key frequency of 40Hz. Members of the labs of Professors Ed Boyden and Alan Jasanoff presented new advances in brain imaging. Members of Professor Manolis Kellis’s lab showed how sophisticated computational approaches can help demystify the genetic complexities of Down syndrome. A poster representing the lab of Professor Ernest Fraenkel highlighted molecular networks related to neurodegeneration. And members of the labs of Professors Ann Graybiel and Matthew Wilson highlighted neural mechanisms fundamental to behavior and memory.

The symposium offered all these scientists, and their hundreds of audience members, the chance to virtually gather and learn from each other at a crossroads of intersecting disease biology.

Upcoming Alana Down Syndrome/Aging Brain Initiative Symposium

Research symposium Oct. 5 & 6th on Glial and Neuronal Biology of the Aging Brain
EventsOctober 5, 2022
Cells labeled in green & blue cluster in interesting 'rosette' patterns
The Alana Down Syndrome Center aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition.
The Aging Brain Initiative is an interdisciplinary effort by MIT focusing on understanding neurodegeneration and discovery efforts to find hallmarks of aging, both in health and disease.
The ADSC and the ABI are teaming up for a joint symposium, focusing on the challenges of aging brains in cognitively normal adults, and the overlap with aging for people with DS.

The topic of this symposium is Glial and Neuronal Biology of the Aging Brain

REGISTER HERE:

Event Registration

 

 

This symposium will take place virtually over the course of two days: October 5 and October 6. The talks on October 5 will take place in the afternoon EST and the October 6 talks will take place in the morning EST. The event is open to the public and free to attend though registration will be required. Be on the lookout for registration emails and more information on this page as the event date approaches.
Confirmed Speakers: