The essential nutrient choline holds promise in helping to protect against Alzheimer’s disease (AD) across several generations, according to a mouse study at Arizona State University (ASU).
Researchers at the Biodesign Institute and ASU-Banner Neurodegenerative Disease Research Center (NDRC) focused on mice bred to display AD-like symptoms. They found that when mice were given high choline in their diet, their offspring showed improvements in spatial memory, compared with those given a normal choline regimen in the womb.
Choline is an essential nutrient naturally present in some foods and also available as a dietary supplement. It is used by the body to produce acetylcholine, an important neurotransmitter essential for brain and nervous system functions including memory, muscle control and mood.
Importantly, the positive effects of choline supplementation appear to be transgenerational, not only protecting mice receiving choline supplementation during gestation and lactation, but also the subsequent offspring of these mice. So while the last generation received no direct choline supplementation, they still reaped the benefits of treatment, likely due to inherited changes in their genes.
Choline acts to protect the brain from Alzheimer’s disease in at least two ways, both of which are investigated in the new study. First, choline lowers homocysteine, an amino acid that can act as a potent neurotoxin, contributing to the hallmarks of AD: neurodegeneration and the formation of amyloid plaques.
Homocysteine doubles the risk of developing Alzheimer’s disease and is found in higher levels in AD patients. Choline performs a chemical transformation, converting the harmful homocysteine into the helpful chemical methionine.
Secondly, choline lowers the activation of microglia, cells that clear away debris in the brain. While their housekeeping functions are important for brain health, activated microglia can get out of control, as they typically do in AD.
Over-activation of microglia leads to brain inflammation and can eventually lead to neuron death. Choline supplementation reins in microglia activity, offering further protection from the ravages of AD.
It is well-established that choline is especially important in early brain development. Pregnant women are advised to maintain choline levels of 550 mg per day for the health of their developing fetus.
“Studies have shown that about 90 percent of women don’t even meet that requirement,” said lead author Ramon Velazquez, Ph.D. “Choline deficits are associated with failure in developing fetuses to fully meet expected milestones like walking and babbling. But we show that even if you have the recommended amount, supplementing with more in a mouse model gives even greater benefit.”
Indeed, when the AD study mice received supplemental choline in their diet, their offspring showed major improvements in spatial memory, which was tested in a water maze. Further examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed the epigenetic alterations induced by choline supplementation.
Choline is an attractive candidate for protection against AD as it is considered a very safe alternative, compared with many pharmaceuticals. The authors note that it takes about 9 times the recommended daily dose of choline to produce harmful side effects.
The researchers stress however that although the findings in mice are promising, a controlled clinical trial in humans will ultimately determine the effectiveness of choline as a potential weapon against Alzheimer’s disease.
“No one has ever shown transgenerational benefits of choline supplementation,” Velazquez said. “That’s what is novel about our work.”
The findings are published in the journal Molecular Psychiatry.
Source: Arizona State University