What Do Cholesterol, Gut Disorders and Alzheimer’s Have in Common? Genes.

One of the largest genetic studies to date revealed extensive genetic links between Alzheimer’s and gut disorders. Cholesterol was a major factor in both.

Alzheimer’s presents many unanswered questions for scientists and patients alike. Why do cholesterol-lowering drugs reduce the risk of developing Alzheimer’s? Why do gut conditions like peptic ulcer disease and gastritis increase the risk of Alzheimer’s? Could the gut be key to treating Alzheimer’s?

A study published in Communications Biology unveiled genetic links between gastrointestinal disorders and cholesterol to Alzheimer’s disease. The study led by Emmanuel Adewuyi, PhD, from Edith Cowan University compared genetic data between 400,000 individuals with gastrointestinal disorders and 400,000 individuals with Alzheimer’s disease, identifying new potential targets for treatment in the process.

“Looking at the genetic and biological characteristics common to AD and these gut disorders suggests a strong role for lipids metabolism, the immune system, and cholesterol-lowering medications,” Adewuyi said. “Whilst further study is needed into the shared mechanisms between the conditions, there is evidence high cholesterol can transfer into the central nervous system, resulting in abnormal cholesterol metabolism in the brain.”

The shared genetics of Alzheimer’s and gut disorders

The researchers found several genetic factors associated with gastroesophageal reflux disease, peptic ulcer disease, and Alzheimer’s. Many of these genes, including phosphodiesterase 4B and CD46, are involved in the brain’s inflammatory response. 

Since the gene CD46 is also involved in killing bacteria linked to peptic ulcers — Helicobacter pylori — the authors believe the bacteria may be involved in Alzheimer’s as well.

“There is also evidence suggesting abnormal blood lipids may be caused or made worse by gut bacteria (Helicobacter pylori), all of which support the potential roles of abnormal lipids in Alzheimer’s disease and gut disorders,” Adewuyi said. “For example, elevated cholesterol in the brain has been linked to brain degeneration and subsequent cognitive impairment.”

Cholesterol-lowering drugs may lower the risk of developing Alzheimer’s and are also beneficial to the gut. Similarly, Mediterranean-style diets, which are known to lower the risk of Alzheimer’s, also impact cholesterol levels in the blood while contributing to overall gut health. Why?

The researchers found that many genes involved in breaking down and using fats are also involved in both Alzheimer’s and gut disorders. Together with the findings relating to the immune system, it suggests that the microbiota — the trillions of bacteria residing in the gut — may also play an important role, since they impact both cholesterol levels and the immune system.   

“This improves our understanding of the causes of these conditions and identifies new targets to investigate to potentially detect the disease earlier and develop new treatments for both types of conditions,” Adewuyi said. 

The authors wrote that drugs affecting fat metabolism, such as lipase inhibitors or statins, could provide better treatments and symptom management for people with both gastrointestinal disorders and Alzheimer’s disease. 

In addition, the study suggests screening people with gastrointestinal disorders for cognitive decline could identify Alzheimer’s disease early.

“These findings provide further evidence to support the concept of the ‘gut-brain’ axis, a two-way link between the brain’s cognitive and emotional centers, and the functioning of the intestines,” the senior author on the study, professor Simon Laws, said.