What is already known
Alzheimer’s disease is a progressive condition that destroys memory and other brain functions, and it is caused by the accumulation of neuroinflammatory proteins such as amyloid beta and tau. Some studies have implicated gut bacteria in the early stages of Alzheimer’s disease, but how the gut microbiota changes before the onset of disease symptoms is unclear.
What this research adds
Researchers examined 164 healthy adults with and without the presence of abnormal amyloid and tau proteins in the brain — a condition known as preclinical Alzheimer’s disease. Compared with controls, people with preclinical Alzheimer’s disease had a different microbiota composition, with higher levels of specific bacterial species and more active microbial pathways involved in the degradation of the amino acids arginine and ornithine. Integrating these features into machine-learning algorithms to predict preclinical Alzheimer’s disease improved the algorithms’ accuracy and sensitivity.
Conclusions
Understanding how gut microbes are linked to preclinical Alzheimer’s disease could help to identify markers of disease risk, which may eventually be used to develop gut-directed interventions to at-risk individuals.
Gut microbes have been linked to several conditions, including neurodegenerative disorders. Now, researchers have found that the presence of certain bacterial species in the gut microbiota may correlate with early signs of Alzheimer’s disease.
The findings, published in Science Translational Medicine, may help to identify markers of Alzheimer’s disease risk, which may be eventually used to develop gut-directed interventions to at-risk individuals.
Alzheimer’s disease is a progressive condition that destroys memory and other brain functions, and it is caused by the accumulation of neuroinflammatory proteins such as amyloid beta and tau. Some studies have implicated gut bacteria in the early stages of Alzheimer’s disease, but how the gut microbiota changes before the onset of disease symptoms is unclear.
To identify microbial signatures of early Alzheimer’s disease, Aura Ferreiro at Washington University School of Medicine in St. Louis, Missouri, and her colleagues set out to examine 164 healthy people aged 68 to 94 over time.
Microbial signature
Study participants regularly underwent a series of tests, including brain imaging, stool sampling, and clinical and cognitive exams. About 30% of participants showed the asymptomatic presence of abnormal amyloid and tau proteins in the brain — a condition known as preclinical Alzheimer’s disease.
Compared with people without abnormal amyloid and tau build-up, those with preclinical Alzheimer’s disease had a different microbiota composition, the researchers found. Species associated with preclinical Alzheimer’s disease included Dorea formicigenerans, Faecalibacterium prausnitzii, Coprococcus catus and Anaerostipes hadrus.
Participants with preclinical Alzheimer’s disease also had more active microbial pathways involved in the degradation of the amino acids arginine and ornithine, the team found.
Disease risk
Next, the researchers integrated these microbiota features into machine-learning algorithms to predict preclinical Alzheimer’s disease. When validated in 65 of the 164 study participants, the algorithms showed improved accuracy and sensitivity.
The findings show that gut bacteria may be linked to preclinical Alzheimer’s disease. However, more work is needed to validate these associations in larger studies and assess whether alterations in the composition of the gut microbiota drive the development of disease.
Identifying microbiota markers in stool may improve early detection of Alzheimer’s disease risk and inform therapies to halt neurodegeneration and cognitive decline, the researchers say. “Whereas mechanisms that govern the impact of the gut on [Alzheimer’s disease] severity and progression have not been fully elucidated, such efforts potentially could lead to gut microbiome–directed interventions that reverse or ameliorate [Alzheimer’s disease] pathology,” the authors say.
