Alzheimer's

Translating Genetic Findings Into Dementia Treatments

Tracing the Path From Bench to Bedside

brain behind DNA molecule

When IRP graduate student Pilar Alvarez Jerez looked at the results of a recent experiment, she noticed that when a particular genetic variant is present in a gene called GBA1, it causes a change in the gene's activity. The GBA1 variant, which is associated with Parkinson’s disease and Lewy body dementia, was discovered last year in people of African ancestry by researchers at NIH’s Center for Alzheimer's and Related Dementias (CARD). It appears to suppress the gene’s ability to make a functional version of an enzyme that helps brain cells recycle their proteins.

“This was an interesting finding, but it still didn’t answer how the variant was functioning to lower enzyme activity,” Pilar says.

From Friend to Foe: When the Immune System Turns on the Brain

IRP Research is Exploring the Role of Immune Cells in Dementia

illustration of fire trucks rushing to put out a fire in the brain

If you visit a lab at NIH’s Center for Alzheimer’s and Related Dementias (CARD), you may find yourself surrounded by several robots hard at work nurturing the hundreds of sets of genetically modified stem cells that CARD scientists use to study the illnesses that give CARD its name. Many of these cells will be coaxed to mature into the neurons that power our movements, thoughts, and memories — but not all of them. Neurons have long received the lion share of dementia researchers’ attention, understandable seeing as the visible symptoms of Alzheimer’s disease are closely linked to a build-up of proteins — amyloid-beta and misfolded tau — that damage neurons. However, neurons aren’t the only brain cells involved in dementia.

Jekyll-and-Hyde Gene Has Dual Influences on Dementia Risk

IRP’s Priyanka Narayan Explores How the ApoE Gene Affects Fat Management in the Brain

two DNA molecules overlaid on top of a brain

Just as Dr. Jekyll and Mr. Hyde exhibited the extremes of good and bad qualities in a single man, IRP Stadtman Investigator Priyanka Narayan, Ph.D., is showing how a single gene can both protect against and raise the risk for Alzheimer’s disease and other dementias. As we observe Alzheimer’s and Brain Awareness month this June, we talked with Dr. Narayan about her work.

“Our research focuses on understanding fundamental cell biology in brain cells and how genetic factors affecting that biology can predispose individuals to Alzheimer's disease,” Dr. Narayan says. “More recently, we’ve become interested in protective factors that make people more resistant to getting Alzheimer’s disease and other forms of neurodegenerative diseases as well.”

Gene Therapy Protects Neurons From Alzheimer’s Disease

New Approach Preserves Cognitive Abilities in Pre-Symptomatic Mice

diagram showing a virus entering a cell and delivering a gene into its nucleus

Cooks preparing traditional holiday feasts will surely find that a fire extinguisher can effectively quench an oven inferno, but it would probably be better if the oven never caught fire in the first place. Similarly, Alzheimer’s researchers have focused much more on putting out the biological fires scorching patients’ brains than on making brain cells ‘fireproof.’ A new IRP study in mice, however, suggests better results might be achieved with an approach specifically designed to make patients’ neurons more resilient.

Data Mining for Dementia Clues

IRP Research Examines Under-Appreciated Factors in Alzheimer’s Disease

brain with red area in the middle representing inflammation

This June, the observance of Alzheimer’s and Brain Awareness month reminds us just how devastating the impact of Alzheimer’s and other dementias is across the world. About 55 million people are currently living with Alzheimer’s disease or related dementias such as frontotemporal dementia and Lewy body dementia. This includes the estimated 6.7 million people in the U.S. over age 65 with Alzheimer’s disease, a population whose cognitive decline imposes huge financial costs on the American economy and often unrecognized burdens on the unpaid family members who provide care for those patients.

While the disease has been a target of intensive investigation ever since Alois Alzheimer first discovered clumps of amyloid beta protein and tangles of tau in the brain of a deceased patient in 1906, scientists have made only modest progress in treating it. Efforts to design drugs targeting the abnormal globs of amyloid and tau thought to cause Alzheimer’s have met with only limited success. That’s why IRP investigator Keenan Walker, Ph.D., is taking a different approach: exploring the link between dementia risk and the immune system.

Poster Sessions Celebrate Summer Science

Annual Event Brandishes the Next Generation of Clinicians and Scientists

Andrés Gorbea, Sarah Bengtson, Lietsel Jones, Michaella Bono, and Joseph Grech

A year after hundreds of high school, undergraduate, and graduate students were only able to participate from afar in NIH’s 2021 Summer Internship Program, IRP researchers were excited to welcome some of the program’s 2022 participants to campus. Regardless of whether they were working in the lab or remotely, these budding scientists received a full-time immersion into the world of IRP science and, surely, learned a great deal from the mentorship of NIH’s many world-renowned researchers.

To celebrate the interns’ hard work, NIH’s Summer Poster Days on August 3 and 4 gave more than 600 of them the opportunity to virtually present posters explaining their projects. With so many bright young men and women displaying the fruits of their scientific labors, it was difficult to select just a handful to highlight in this blog. Read on to learn about how five of NIH’s 2022 summer interns shed light on topics from the microbes living on our skin to the blood-clotting platelets that flow through our veins.

Poster Days Spotlight Young Researchers

Budding Scientists Showcase Research at Annual Event

Yasmin Ali

Any scientist who wants to make game-changing discoveries has to start somewhere — even Albert Einstein worked in a patent office before landing his first job in academia. Through its Postbaccalaureate IRTA program, NIH hopes to give aspiring scientists more of a leg up than Einstein had by bringing them into IRP labs after they complete their undergraduate studies.

On April 26, 27, and 28, more than 900 recent college graduates participating in the program presented at this year’s virtual Postbac Poster Days. Read on to learn about a few of these young researchers and their contributions to the groundbreaking work being done at NIH.

An Unlikely Target in the Fight Against Alzheimer’s

IRP Researchers Find Link Between Dementia and Byproducts of Cholesterol Breakdown

old man in nursing home

When most people think about Alzheimer’s disease, the liver is probably the organ least likely to come to mind. Yet recent IRP research suggests that molecules called bile acids, which are synthesized in the liver, may influence the development of Alzheimer’s disease. In honor of Brain Awareness Week this week, we’re diving into that work to learn how such an unlikely target could help lead to new treatments for Alzheimer’s and other forms of dementia.

To date, efforts to develop therapies for Alzheimer’s disease, which affects more than 6 million Americans over the age of 65, have achieved little success. Many scientists are focused on proteins in the brain as potential treatment targets, including the ‘amyloid-beta’ protein now infamous amongst Alzheimer’s researchers. In contrast, IRP senior investigator Madhav Thambisetty, M.D., Ph.D., has been exploring the role that cholesterol might play in the development of Alzheimer’s and vascular dementia, which is marked by microscopic bleeding and blood vessel blockage and is the second most common form of dementia.

Experimental Compound Supercharges Cellular Power Plants

Treatment Approach Could Combat Obesity and Its Consequences

light bulb

When your phone or laptop is low on power, you simply connect it to a charger and find the nearest electrical outlet, but the process of restoring lagging energy production in our cells is not nearly as simple. However, a new IRP study has identified a promising approach for doing just that, which could lead to new treatments for obesity and related metabolic ailments like heart disease and diabetes.

Alzheimer’s Patients Show Traces of Cellular Batteries in Blood

Biomarker Discovery Could Aid Diagnosis and Therapeutic Development

extracellular vesicles containing genetic material

Our cells can’t afford to be wasteful, so they prefer to recycle broken components. However, when the mitochondria that provide their energy are damaged beyond repair, cells may have no choice but to throw them out. New IRP research suggests that more of this mitochondrial debris floats in the blood of patients with Alzheimer’s disease, potentially providing an easy, cost-effective way to diagnose or even possibly predict the illness.