An estimated 76,000 Oklahomans live with Alzheimer’s disease, a number that has risen by 13% in just five years. Despite the increasing need for effective treatments, therapies for age -related dementia have largely not delayed or stopped the progression of the disease.
Now, a researcher from the University of Oklahoma, supported by $ 2.2 million in federal financing, is leading to efforts to unravel the mysteries of cognitive decline in aging if possible to open the door to new life-changing drugs in the process.
Most treatments for using Alzheimer’s use antibodies to focus on a pathogen protein that is deposited in the brain, but that approach is too late in the game. Once you have lost neurons on disease progression, you can’t get them back. “
Sreemathi Logan, Ph.D., university lecturer, Biochemistry department and physiology, OU College of Medicine
“Our work is intended to offer alternative strategies for identifying and focusing Alzheimer’s and other cognitive impairment,” she said.
Aging is the largest risk factor for dementia, but the mechanisms that link aging to Cognition departure are largely unknown. To gain insight into how this process works, Logan studies molecular variations in the brain of older mice that can be translated into people.
Logan and colleagues of the Oklahoma Center for Geroscience and Healthy Brain Aging developed a nightly test model to re -assess the ability of an animal to re -assess a simple task.
By using a specially designed cage, the researchers could observe how mice behave in a motivated learning and memory task through an experiment of four nights. While younger mice easily adapt to changes in spatial learning, a lot of struggling, but not all, older mice. By dividing older mice into cognitive “intact” and “reduced” subgroups, the researchers then study the brains of the reduced mice. This is an important aspect of testing when it translates to people: not all elderly individuals experience cognitive decline, but many experience the debilitating state of dementia in old age.
A focus of the subsidy is to understand the mechanism of astrogliosis, an abnormal increase in the number of astrocytes – special cells in the brain that are crucial for maintaining the health of neurons – while aging. An important research question is whether disorders in the mitochondrial function of astrocytes reactive astrogliosis associated with cognitive disorders drive.
Logan and members of her lab are working on this research question in collaboration with the Geroscience Center of Biomedical Research Excellence and the Oklahoma Nathan Shock Center, both at the OU Health Sciences Campus and the Oklahoma Medical Research Foundation.
“Changes in astrocyte metabolism can seriously influence how neurons communicate that influence cognition and other functions,” Logan said.
The aim of the researchers is to identify specific markers in the old astrocytes that may be aimed at inhibitors or activators of small molecules, so that they can promote cognition. Such an approach would deviate from current antibody-based therapies.
“We look at overexpression of goal proteins that can benefit astrocyte metabolism and see if that improves cognition,” Logan said. “That is a road that we try to take to see how we can intervene in cells to improve cognition as we get older.”
Logan’s research has attracted interest from other financiers, including the Hondution Foundation, a non -profit organization that works on improving aging research. That work aims to understand the metabolic factors, including obesity, that influence the age -related cognition.
With this new price and five-year subsidy from the National Institute of Aging-Wil Logan, the relevant mechanisms that stimulate dementia in older adults and ultimately inspire the development of new treatments for these devastating circumstances.
Care for dementia patients has steep costs. In Oklahoma, almost 11% of residents older than 65 live with Alzheimer’s, slightly more than the national average. Because most people with Alzheimer’s live at home, more than 108,000 caregivers in the entire state are the heavy responsibility of daily care on a crack. According to the Alzheimer’s Association, this care burden is the equivalent of $ 3 billion in unpaid nursing.
“We try to look at an earlier time in the disease process so that we can intervene,” Logan said, adding that her study is the first to tackle the molecular determining heterogeneity – the inequality in the cognitive function – in aging. This work in the Logan Lab is coordinated by Matthew Baier, a doctoral student in biochemistry and physiology at the OU College of Medicine.
“If we can identify the metabolic paths within astrocytes of people with cognitive dysfunction, we can also identify specific protein goals that influence cognition in older brains. That would be a game change.”