People in the earliest stage of Alzheimer’s disease (AD), after brain changes have begun but before cognitive symptoms become apparent, harbour an assortment of bacteria in their intestines that differs from the gut bacteria of healthy people, according to a new study by researchers at Washington University School of Medicine in St. Louis, USA, published in the journal Science Translational Medicine. During the early stage of AD, which can last two decades or more, affected people accumulate clumps of the proteins amyloid beta and tau in their brains, but do not exhibit signs of neurodegeneration or cognitive decline. Scientists already know that the gut microbiomes of people with symptomatic AD differ from the microbiomes of healthy people of the same age. But, this new study looks specifically at the gut microbiomes of people in the critical pre-symptomatic phase.
To distinguish participants already in the early stage of AD from those who were healthy, the researchers looked for signs of amyloid beta and tau accumulation through brain scans and cerebrospinal fluid. Of the 164 participants, about a third (49) had signs of early AD. An analysis revealed that healthy participants and those with preclinical AD had markedly different gut bacteria, in terms of the species of bacteria present and the biological processes in which those bacteria are involved, despite eating a very similar diet. These differences correlated with amyloid and tau levels, which rise before cognitive symptoms appear, but did not correlate with neurodegeneration, which becomes evident about the time cognitive skills start to decline. These differences could potentially be used to screen for early AD, the researchers said.
A limitation of this study, the researchers noted, is that the gut microbiome can change over time, but stool samples were collected just once. As such, they highlighted a need for future studies that sample the gut microbiome at multiple points in time. The fact that not everyone with preclinical AD will actually develop disease symptoms in their lifetime also stresses the need for further long-term studies, the team noted. They also emphasised that, while these data suggest that the gut microbiome is dysregulated in the early stages of AD, it is unclear whether this finding is a cause or consequence of the disease. If it turns out that the gut is influencing the brain to help drive AD, it might open the door to new treatment strategies and with this in mind, the researchers have launched a five-year follow-up study designed to figure out whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD. Read the study, in Science Translational Medicine: https://doi.org/10.1126/scitranslmed.abo2984
