The brains of people with Alzheimer’s disease appear to show both increased bacterial populations and different proportions of specific bacteria compared to healthy brains, according to a new U.K. study which used DNA sequencing to evaluate the postmortem brains of Alzheimer’s patients.
The new findings, published in the journal Frontiers in Aging Neuroscience, support growing evidence that bacterial infection and inflammation in the brain may play a role in Alzheimer’s disease, a severe neurodegenerative condition that leads to cognitive decline, and eventually death.
“Alzheimer’s brains usually contain evidence of neuroinflammation, and researchers increasingly think that this could be a possible driver of the disease, by causing neurons in the brain to degenerate,” said study author Dr. David Emery at the University of Bristol.
But what exactly is causing this inflammation? Some genetic risk-factors for Alzheimer’s disease can have effects on the inflammatory response, but infection may also play a role.
“Neuroinflammation in the brain may be a reaction to the presence of bacteria,” said Emery.
A healthy brain is sealed behind specialized blood vessels that make it very difficult for bacteria in the blood to enter. However, certain genetic risk-factors for Alzheimer’s disease may cause these blood vessels to lose some of their integrity, potentially allowing bacteria to enter and colonize the brain.
For the study, the researchers investigated whether there were any differences in the types of bacteria present in brains from Alzheimer’s disease patients and healthy brains.
“Previous studies looking at bacteria in the Alzheimer’s brain have primarily investigated specific bacterial species,” said Dr. Shelley Allen, another researcher involved in the study.
“We wanted to use an unbiased method to obtain the fullest overview possible of the entire bacterial population in the Alzheimer’s brain, and compare these results with those from a healthy aged brain.”
The research team analyzed eight Alzheimer’s and six healthy brain samples from a brain bank, where people donate their brains after death for medical research. They used a technique called next generation sequencing (NGS) to detect specific bacterial genes.
“NGS technology allows millions of these DNA molecules to be sequenced at the same time, providing an unbiased overview of a complex bacterial population,” said Allen.
The researchers found that the Alzheimer’s brains contained different proportions of specific bacteria compared with the healthy brains.
“Comparing the bacterial populations showed at least a tenfold higher ratio overall of Actinobacteria (mostly P. acnes) to Proteobacteria in the Alzheimer’s brain compared with the healthy brain,” said Emery.
However, they were surprised to discover that there also appeared to be more bacteria in the Alzheimer’s brains.
“Unexpectedly, Alzheimer’s brains gave on average an apparent 7-fold increase in bacterial sequences above that seen in the healthy brain,” said Allen. “The healthy brains yielded only low levels of bacterial sequences, consistent with either a background signal or normal levels present in the blood stream in brain tissue.”
The researchers warn that the NGS technique does not directly indicate bacterial numbers, and more studies are needed to confirm that bacteria play an active role in the disease.
“We need quantitative studies on the bacterial presence in the brain,” said Allen. “Larger numbers of brain samples are required, and future studies should also investigate if bacteria are involved in other neurodegenerative diseases involving neuroinflammation.”