Nav: Home

New diagnostic techniques and drug may slow and even reverse cognitive decline from aging

December 04, 2019

BEER-SHEVA, ISRAEL and BERKELEY, CALIFORNIA...DECEMBER 4, 2019 - A groundbreaking clinical approach has been developed combining new diagnostic techniques to detect a leaking blood-brain barrier (BBB) with a new anti-inflammatory drug that for the first time slows or reverses age-related cognitive decline.

In two related studies published in the journal Science Translational Medicine, researchers from Ben-Gurion University of the Negev (BGU) and the University of California, Berkeley (UC) report that when given the new drug to reduce inflammation, senile mice had fewer signs of dysfunctional brain electrical activity and were better able to learn new tasks, becoming almost cognitively adept as mice half their age.

Other findings indicate two practical pathways -- measuring the leakiness of the blood-brain barrier via MRI and abnormal electrical brain activity via EEG -- that can be used to screen people for a leaky BBB.

"These findings represent real hope that we can stop, and even reverse, the deterioration that until now we considered an inevitable part of aging," said senior study author BGU Prof. Alon Friedman M.D., Ph.D., and research partner Prof. Daniela Kaufer, UC Berkeley Department of Integrative Biology. "It is the first diagnostic, coupled with personalized drug intervention targeting the BBB."

"We tend to think about the aged brain in the same way we think about neurodegeneration: age involves loss of function and dead cells," said Kaufer. "But our new data tell a different story about why the aged brain is not functioning well -- it is because of this 'fog' of inflammatory load. But when you remove that inflammatory fog, within days the aged brain acts like a young brain. It is an extremely optimistic finding in terms of the capacity for plasticity that exists in the brain and indicates that we can reverse brain aging."

The BBB is a semi-permeable interface that separates circulating blood from the brain. It also prevents the transfer of unwanted molecules or infectious organisms from the blood to the brain. Increasing evidence shows that breaching the integrity of this barrier causes many brain diseases and neurodegeneration as a result of aging.

In analyzing brain tissue from humans, Kaufer found evidence of albumin in aged brains as well as increased neuroinflammation and production of TGF-β, a protein that controls cell growth.

Because albumin is typically synthesized only outside the BBB, increased albumin within the brain indicates BBB damage leading to inflammation.

Profs. Kaufer and Friedman also showed that introducing albumin into the brain can, within a week, make the brains of young mice look like those of old mice, in terms of neuronal functions and their susceptibility to seizures. These albumin-treated mice also navigated a maze as poorly as aged mice.

The Friedman group in the BGU Brain Imaging Center developed an MRI imaging protocol -- dynamic contrast-enhanced (DCE) imaging -- and mathematical algorithms that quantify leakage in the BBB.

"When we infuse albumin into the brains of young mice, we recapitulate aging of the brain: the gene expression, the inflammatory response, resilience to induced seizures, mortality after seizures, and performance in a maze. And when we record their brain activity, we find these paroxysmal slow wave events (PSWE)," Kaufer said. "And all is specific to the site we infuse, so doing this is sufficient to get an aged phenotype of this very young brain."

Administering a new anti-inflammatory drug that specifically targets TGF-β signaling decreased the PSWE occurrences in BBB leakiness. The drug, a small molecule called IPW, not only helps to alleviate the effects of a leaky BBB but seems to also heal the barrier. "These PSWEs may explain some of the symptoms we see in Alzheimer's disease patients and therefore lowering the PSWE burden may help those patients," said Dr. Dan Milikovsky who led the project in Prof. Friedman's laboratory.

"Together, the evidence points to a dysfunction in the brain's vasculature as one of the earliest triggers of neurological aging," Friedman said. "This combination of two biomarkers and a drug gives us the innovative ability to diagnose and treat patients with blood-brain barrier leakiness, and cease treatment once the BBB closes and danger decreases."

Kaufer added, "We got here through this back door starting with questions about plasticity having to do with the blood-brain barrier, traumatic brain injury and how epilepsy develops. But after we'd learned a lot about the mechanisms, we started thinking that maybe in aging it is the same story. This is new biology, a completely new angle on why neurological function deteriorates as the brain ages."

The researchers have started a company to develop IPW and other therapeutics with the goal of reducing brain inflammation, and thus permanent damage, after stroke, concussion or traumatic brain injury. The drug may eventually help older adults suffering from early dementia or Alzheimer's disease with demonstrated BBB leakage.
This work was supported by the National Institutes of Health (R01NS066005, R56NS066005), Bakar and Archer Foundations, European Union's Seventh Framework Program, Israel Science Foundation, and the Binational Israel-USA Science Foundation.

American Associates, Ben-Gurion University of the Negev

American Associates, Ben-Gurion University of the Negev (AABGU) plays a vital role in sustaining David Ben-Gurion's vision: creating a world-class institution of education and research in the Israeli desert, nurturing the Negev community and sharing the University's expertise locally and around the globe. As Ben-Gurion University of the Negev (BGU) looks ahead to turning 50 in 2020, AABGU imagines a future that goes beyond the walls of academia. It is a future where BGU invents a new world and inspires a vision for a stronger Israel and its next generation of leaders. Together with supporters, AABGU will help the University foster excellence in teaching, research and outreach to the communities of the Negev for the next 50 years and beyond. Visit to learn more. AABGU, headquartered in Manhattan, has nine regional offices throughout the United States. For more information visit

American Associates, Ben-Gurion University of the Negev

Related Aging Articles:

A new biomarker for the aging brain
Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified changes in the aging brain related to blood circulation.
Scientists invented an aging vaccine
A new way to prevent autoimmune diseases associated with aging like atherosclerosis, Alzheimer's disease, and Parkinson's disease was described in the article.
The first roadmap for ovarian aging
Infertility likely stems from age-related decline of the ovaries, but the molecular mechanisms that lead to this decline have been unclear.
Researchers discover new cause of cell aging
New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works.
Deep Aging Clocks: The emergence of AI-based biomarkers of aging and longevity
The advent of deep biomarkers of aging, longevity and mortality presents a range of non-obvious applications.
Intelligence can link to health and aging
For over 100 years, scientists have sought to understand what links a person's general intelligence, health and aging.
Putting the brakes on aging
Salk Institute researchers have developed a new gene therapy to help decelerate the aging process.
New insights into the aging brain
A group of scientists at the Gladstone Institutes investigated why the choroid plexus contains so much more klotho than other brain regions.
We all want 'healthy aging,' but what is it, really? New report looks for answers
Led by Paul Mulhausen, MD, MHS, FACP, AGSF, colleagues from the American Geriatrics Society (AGS) set looking critically at what 'healthy aging' really means.
New insight into aging
Researchers at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University examined the effects of aging on neuroplasticity in the primary auditory cortex, the part of the brain that processes auditory information.
More Aging News and Aging Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.