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.”
Learn more: Temple Researchers Successfully Reverse Cognitive Impairments in Mice with Dementia
The Latest on: Dementia
[google_news title=”” keyword=”dementia” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Dementia
- ITV Loose Women star Coleen Nolan shares her dementia fears as amid menopause changeson April 27, 2024 at 11:59 am
Loose Women star Coleen Nolan admits the fear of seeing her mother deteriorate with dementia left her fearing the worst when hormonal changes left her with 'brain fog' ...
- Grandfather with dementia refuses his medicationson April 27, 2024 at 6:46 am
As with most things regarding dementia, it usually works best to try to figure out what’s behind the person’s behavior. One common issue is feeling a lack of control.
- Man with dementia says diagnosis not end of worldon April 27, 2024 at 3:31 am
A member of a dementia community group has said that being diagnosed with the condition is not the "end of the world". Neil McKellar, who is part of Dementia Friendly Sandbach, which is based in ...
- Dementia in Children: Unlocking Hope with Novel Researchon April 27, 2024 at 2:50 am
Although the causes differ from dementia acquired later in life, the progressive nature of the illness is the same.Half of infants and children diagnosed with childhood dementia will not reach their ...
- Search Intensifies for Missing 83-Year-Old Woman with Dementia in Fort Lauderdaleon April 26, 2024 at 11:51 pm
Fort Lauderdale Police are searching for Collene Ross, 83, who suffers from dementia and was reported missing Thursday.
- Dementia May Be Underdiagnosed in States With Motor Vehicle Reporting Mandateson April 26, 2024 at 2:26 pm
An estimated 17.0% of primary care clinicians underdiagnosed dementia in states with clinician reporting mandates -- more than twice the rate than in states with driver self-reporting mandates (7.1%) ...
- His daughter whispers, ‘Where are your paychecks?’ in his ear. My stepfather is in a nursing home with dementia. How can my mother and I protect him?on April 26, 2024 at 1:36 pm
My mother has a durable power of attorney for Sam’s healthcare and is his primary representative. No one has financial POA.” ...
- Oasis Or Mirage? Digital Dementia Screening In The Neurology Deserton April 26, 2024 at 12:44 pm
Diagnosis of Alzheimer's and related dementias is broken. As blood tests emerge, what is the role of digital screening tools and neurotechnologies in clinical practice?
- How to Help Your Loved One Navigate the Costs of Dementia Careon April 25, 2024 at 2:25 pm
Dementia is a progressive disease, meaning that your loved one will need more care over time. In the beginning, you can save money on care expenses with technology. This might include things like ...
via Bing News