Reversing memory deficits and impairments in spatial learning is a major goal in the field of dementia research. A lack of knowledge about cellular pathways critical to the development of dementia, however, has stood in the way of significant clinical advance. But now, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) are breaking through that barrier. They show, for the first time in an animal model, that tau pathology – the second-most important lesion in the brain in patients with Alzheimer’s disease – can be reversed by a drug.
“We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits,” explained senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer’s Center at Temple at LKSOM. The study, published online in the journal Molecular Neurobiology, raises new hope for human patients affected by dementia.
The researchers landed on their breakthrough after discovering that inflammatory molecules known as leukotrienes are deregulated in Alzheimer’s disease and related dementias. In experiments in animals, they found that the leukotriene pathway plays an especially important role in the later stages of disease.
“At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage,” Dr. Praticò said. “Having discovered this, we wanted to know whether blocking leukotrienes could reverse the damage, whether we could do something to fix memory and learning impairments in mice having already abundant tau pathology.”
To recapitulate the clinical situation of dementia in humans, in which patients are already symptomatic by the time they are diagnosed, Dr. Praticò and colleagues used specially engineered tau transgenic mice, which develop tau pathology – characterized by neurofibrillary tangles, disrupted synapses (the junctions between neurons that allow them to communicate with one another), and declines in memory and learning ability – as they age. When the animals were 12 months old, the equivalent of age 60 in humans, they were treated with zileuton, a drug that inhibits leukotriene formation by blocking the 5-lipoxygenase enzyme.
After 16 weeks of treatment, animals were administered maze tests to assess their working memory and their spatial learning memory. Compared with untreated animals, tau mice that had received zileuton performed significantly better on the tests. Their superior performance suggested a successful reversal of memory deficiency.
To determine why this happened, the researchers first analyzed leukotriene levels. They found that treated tau mice experienced a 90-percent reduction in leukotrienes compared with untreated mice. In addition, levels of phosphorylated and insoluble tau, the form of the protein that is known to directly damage synapses, were 50 percent lower in treated animals. Microscopic examination revealed vast differences in synaptic integrity between the groups of mice. Whereas untreated animals had severe synaptic deterioration, the synapses of treated tau animals were indistinguishable from those of ordinary mice without the disease.
“Inflammation was completely gone from tau mice treated with the drug,” Dr. Praticò said. “The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed.”
The study is especially exciting because zileuton is already approved by the Food and Drug Administration for the treatment of asthma. “Leukotrienes are in the lungs and the brain, but we now know that in addition to their functional role in asthma, they also have a functional role in dementia,” Dr. Praticò explained.
“This is an old drug for a new disease,” he added. “The research could soon be translated to the clinic, to human patients with Alzheimer’s disease.”
Receive an email update when we add a new DEMENTIA article.
The Latest on: Dementia
via Google News
The Latest on: Dementia
Police: Connecticut Man With Dementia Causes Wrong-Way Crash
on December 19, 2018 at 5:57 am
New York State Police say an 82-year-old Connecticut man with dementia caused a three-vehicle crash by driving the wrong way on a Long Island parkway. WANTAGH, N.Y. (AP) — New York State Police say an ... […]
Missing Conn. Man With Dementia Caused Wrong-Way Crash On LI: PD
on December 19, 2018 at 5:52 am
An elderly man who was reported missing in Connecticut caused a wrong-way crash on the Wantagh State Parkway Tuesday night, state police say, seriously injuring himself and also injuring three others. […]
MacMaster holiday concert billed as dementia-inclusive
on December 19, 2018 at 5:44 am
TORONTO — A holiday concert by fiddlers Natalie MacMaster and Donnell Leahy is being billed as dementia-inclusive, for providing audience members with large-font printed lyrics, ear plugs and fidget t... […]
Assisted Living’s Breakneck Growth Leaves Safety Of Dementia Patients Behind
on December 19, 2018 at 2:01 am
Insight provides an in-depth look at health care issues in and affecting California. Have a story suggestion? Let us know. They found Bonnie Walker’s body floating in a pond behind her assisted living ... […]
Missing Woman With Dementia Found Dead By Banks Of Willamette
on December 18, 2018 at 8:52 pm
PORTLAND, OR – The 76-year-old woman with dementia who went missing on Saturday, was found dead on Tuesday. Marie Helena Evans was found dead by the banks of the Willamette River, not far from ... […]
Most caregivers of people with dementia are family members, and they need help
on December 18, 2018 at 2:56 pm
Family care of an older adult has emerged as an essential element of the U.S. health care system, with 83 percent of long-term care provided to older adults coming from family members or other unpaid ... […]
Assisted living facilities struggle to meet the needs of dementia patients
on December 18, 2018 at 1:49 pm
They found Bonnie Walker’s body floating in a pond behind her assisted living facility in South Carolina. There were puncture wounds on her ear, her temple, her jaw and her cheeks. Her right ... […]
Worldwide Dementia Rates More Than Doubled Over 26-Year Span
on December 18, 2018 at 10:20 am
Rates of dementia worldwide more than doubled from 1990 to 2016, mainly due to population aging, a new report from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 Dementia C... […]
Genetic cause of ALS and frontotemporal dementia blocked by RNA-binding compound
on December 18, 2018 at 7:18 am
Scripps Research Chemistry Professor Matthew Disney, PhD, goes over a formula in his lab. His group at Scripps Research in Jupiter, Florida has made a potential drug that stops ALS, in early studies. […]
via Bing News