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Early Alzheimer's Linked to Gut Microbiome Changes

<ѻý class="mpt-content-deck">— Findings may help identify Alzheimer's disease long before cognitive changes emerge
MedpageToday
A computer rendering of the gut microbiome.

Changes in gut bacteria were linked with very early Alzheimer's disease, cross-sectional data showed.

Gut microbial profiles of cognitively normal people with preclinical Alzheimer's disease -- defined as asymptomatic abnormal brain amyloid -- were distinct from those of individuals without preclinical Alzheimer's, reported Beau Ances, MD, PhD, and Gautam Dantas, PhD, both of Washington University School of Medicine, and co-authors.

Change in gut microbiome composition correlated with amyloid-beta and tau pathological biomarkers but not with markers of neurodegeneration, the researchers said in .

While previous studies have reported gut microbial alterations in , this study showed changes in preclinical disease, Ances noted.

"This was surprising to us as it suggests there are already changes within the gut very early on in the disease process, which could have important implications for biomarker development as well as potential therapies," he told ѻý.

Whether the gut affected the brain or the brain affected the gut wasn't clear. The study didn't examine what led to the changes, but "we are very interested in the role of inflammation," Ances said.

"The observed increase with certain species within the gut could lead to breakdown in the gut epithelium with subsequent inflammation," he pointed out.

"This inflammation may be deleterious," he added. "There is a growing body of evidence that suggests it's not only the presence of amyloid and tau, but also inflammation, that may lead to the changes in the brain."

Ances and colleagues studied a Knight Alzheimer's Disease Research Center (ADRC) cohort of 164 cognitively normal individuals with and without preclinical Alzheimer's disease. Participants were 68 to 94 years old and 45% were male.

Participants had PET and MRI imaging, lumbar puncture to obtain cerebrospinal fluid (CSF) samples, stool sampling, and clinical and cognitive tests, including Clinical Dementia Rating (CDR) evaluations.

Preclinical Alzheimer's was defined as a CDR score of 0 (cognitively normal) and amyloid positivity based on PET or CSF. Based on these criteria, 115 participants were classified as healthy and 49 were classified as having preclinical Alzheimer's disease.

To account for the effect of diet on the microbiome, the researchers assessed nutritional data from stool-matched 24-hour diet logs and found no significant differences in overall calorie intake, caloric source distribution, or intake of any major nutrients between groups.

Stool samples showed both global and specific differences in the gut microbiome. Species most associated with preclinical Alzheimer's status included Dorea formicigenerans (coefficient=0.661) and Oscillibacter sp. 57_20 (coefficient=0.512; P<0.001 for both). Of the taxa significantly associated with preclinical Alzheimer's disease, Alistipes, Barnesiella, and Odoribacter previously were reported in people with symptomatic Alzheimer's patients.

People with preclinical Alzheimer's also had more active microbial pathways involved in the degradation of arginine (coefficient=0.967) and ornithine (coefficient=0.625; P<0.001 for both).

When tested on a subset of 65 participants, the inclusion of specific microbiome features improved the accuracy, sensitivity, and specificity of a machine-learning model for predicting preclinical Alzheimer's status.

Microbiome markers in stool might complement early screening measures for preclinical Alzheimer's and generate new hypotheses about the potential roles of the gut in Alzheimer's progression, the researchers noted.

Adding a relatively simple measure of the gut microbiome can be done very easily in a large group of people, Ances observed.

"Future longitudinal studies need to be performed," he said. "These results could suggest that certain therapies or changing the gut microbiome -- either through probiotics or fecal transplant -- could affect hallmarks of Alzheimer's disease. Future studies may pursue these avenues."

  • Judy George covers neurology and neuroscience news for ѻý, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.

Disclosures

This research was supported by the Infectious Diseases Society of America Foundation, the National Institute on Aging, the Brennan Fund, the Riney Fund, and the Washington University Digestive Diseases Research Core Center.

Ances had no disclosures. Co-authors reported several relationships with industry and nonprofit organizations.

Primary Source

Science Translational Medicine

Ferreiro AL, et al "Gut microbiome composition may be an indicator of preclinical Alzheimer's disease" Sci Transl Med 2023; DOI: 10.1126/scitranslmed.abo2984.