USC researchers potentially reverse Alzheimer’s symptoms in mice
A diet containing compounds found in green tea and carrots reversed Alzheimer's-like symptoms in mice genetically programmed to develop the disease, according to a new study by researchers from the University of Southern California in Los Angeles, and published in the Journal of Biological Chemistry.
Researchers strongly emphasize that the study, which the university announced yesterday, was only in mice, and many mouse models do not translate into human treatments. However, the findings, they say, initially support the idea that certain readily available, plant-based supplements might offer protection against dementia in humans, and that combination therapy may offer the best approach to treating individuals living with Alzheimer's disease.
Combination therapy for Alzheimer’s disease has garnered attention following a recent National Institute on Aging mandate, but this approach has not yet been fully validated, according to researchers.
In this study, researchers looked at two promising nutraceuticals with complementary anti-amyloidogenic properties, the plant-derived phenolics epigallocatechin-3-gallate (EGCG), an α-secretase activator found in green tea, and ferulic acid (FA), found in carrots, tomatoes, rice, wheat, and oats.
The researchers used 32 randomly assigned transgenic mice expressing mutant human amyloid β-protein precursor and presenilin 1 (APP/PS1) to model cerebral amyloidosis, which results in Alzheimer’s-like symptoms. For comparison, each group also contained an equal number of healthy mice.
When the mice were 12 months of age, researchers orally administered 30 milligrams per kilogram of body weight of EGCG, FA, or a combination of both daily for three months. After three months, mice who received the combined EGCG and FA treatment reversed cognitive impairment in most tests of learning and memory, including novel object recognition and maze tasks.
In addition, EGCG- and FA-treated APP/PS1 mice exhibited improvements in brain parenchymal and cerebral vascular β-amyloid deposits and decreased abundance of amyloid β-proteins, compared with either EGCG or FA single treatment, according to the study.
Combined treatment also elevated nonamyloidogenic soluble APP-α and α-secretase candidate and down-regulated amyloidogenic soluble APP-β, β-C-terminal APP fragment, and β-secretase protein expression, providing evidence for a shift toward nonamyloidogenic APP processing. Additional beneficial effects included reduced neuroinflammation, oxidative stress, and synaptotoxicity, researchers found.
“Our findings offer preclinical evidence that combined treatment with EGCG and FA is a promising [Alzheimer’s disease] therapeutic approach,” said senior author Terrence Town, PhD, a professor of physiology and neuroscience at the Keck School of Medicine of USC's Zilkha Neurogenetic Institute.
While it’s not entirely clear why these compounds restored working memory and cognitive function in mice, one mechanism appeared to be the substances' ability to prevent amyloid precursor proteins from breaking up into the smaller proteins called amyloid beta that gum up Alzheimer patients' brains, according to Town in the university statement. The compounds also appeared to reduce neuroinflammation and oxidative stress in the brain, which are key aspects of Alzheimer's disease pathology in humans, he said.
Town said he and his lab will continue exploring combination treatment, with a focus on plant-derived substances that inhibit production of the sticky amyloid beta plaques.