Alzheimer’s disease may leave early signs in the gut, study finds

New imaging technology has uncovered hidden bowel changes in Alzheimer’s, which reveals a potential intestinal resilient connection that can cause a revolution in the early diagnosis and treatment.

Study: Research into intestinal changes in Alzheimer’s disease: in-depth analysis with micro and Nano-3D X-ray phase Contrast tomography. Image Credit: Marko Aliaksandr / Shutterstock

Alzheimer’s disease has more than 30 million people around the world, but the factors that underlie its etiology remain unclear. Recent research is used to the intestines and investigates his potential role in the progress of Alzheimer’s. Published in a recent study in the magazine Science is progressingA team of researchers from Italy and France used advanced imaging techniques to explore the intestinal brain axis and discovered significant bowel changes in three different mouse models of Alzheimer’s disease, causing light to shed on the complex nature of the disease.

Background

Alzheimer’s disease is the main cause of dementia and is characterized by cognitive decline and deterioration of the brain. Despite extensive research, the precise causes of this remain unclear and the current treatments offer limited lighting. Recent studies have emphasized the intestinal-brainSAS that links intestinal health and brain function-and a potential contribution to Alzheimer’s disease.

The intestinal microbiome plays a crucial role in maintaining overall health and is linked to cognitive function. Although research from the past suggests that dysbiosis – an imbalance in intestinal bacteria – can influence the progression of Alzheimer’s, this specific study was aimed at structural and cellular changes in the gut instead of microbial composition. Proof also suggests that disruptions in intestinal microbiota can promote inflammation and achieve harmful bacteria to reach the brain.

Furthermore, changes in intestinal morphology have been observed in patients with Alzheimer’s disease and animal models, which suggests a possible connection between intestinal health and neurodegeneration.

About the study

With the hope that understanding these interactions between the intestinal microbiome and the brain can open new ways for early diagnosis and innovative treatments for Alzheimer’s disease, the current study of Alzheimer’s disease models investigated with the help of advanced imaging techniques, in particular both both Micro and nano three-dimensional (3D) X-ray-contrast tomography (XPCT), a breakthrough image method that is able to be able to do non-invasive structural visualization with high resolution.

The research team investigated the intestine of three different mouse models of Alzheimer’s disease: App/PS1 and App23 mice, which bear human genetic mutations related to family Alzheimer’s and the SAMP8 model, which imitates sporadic, age-related neurodegeneration. These were compared with healthy checks. The Ileum, part of the small intestine, was chosen because of the previously observed involvement in the pathology of Alzheimer’s.

The XPCT method provided non-invasive, high resolution, three-dimensional imaging, whereby complicated details of intestinal structures are unveiled without requiring tissue coloring or sections. Various resolutions were used to capture detailed anatomical structures, from cellular to the whole of the entire organ. In addition, the imaging process included the recording of thousands of projections, which were then reconstructed in 3D volumes for analysis. This approach made visualization of intestinal characteristics possible such as villi, crypts and various cell types, including paneth and cup cells.

Moreover, this study was one of the first to use XPCT to identify changes in telocytes, a type of interstitial cell that is involved in tissue recovery, indicating disruptions in intestinal homeostasis in Alzheimer’s disease. The XPCT also allowed the identification of components of the enteric nervous system, such as the myentic and submucosal plexuses. In addition, the study gave new insights into immune response in Alzheimer’s disease by investigating Peyer’s patches and isolated lymphoid follicles, important intestinal-associed lymphoid tissues involved in immune monitoring.

Nano-XPCT analysis of the paneth and cup cells. ((A) Representative 3D display of the longitudinal representation of one crypt from SAMR1 -Muis. The epithelial layer of the crypt is shown green. The paneth cells are colored yellow and the cup cells in blue. Scale beams, 5 μm. ((B) And (C) Show 3D renderings and nano-xpct-up-ups of Goblet and Paneth cells respectively. The same color code of (A) has been used for the 3D views that are shown in (B) and (C). In detail, the cup cell center is colored in dark blue and the apical part, expanded with mucin -separating granules, which extend to the intestinal lumen, is displayed in light blue. The Paneth cell presents the typical pyramidal form with in principle situated core (blue) and prominent apical granules (yellow) that occupy most of the cytoplasmic area. Nano-xpCT-Close-ups in (B) show goblet cells (indicated by arrows) that separate mucus (asterisks) into the intestinal lumen. Scale beams, 2.5 μm. In (c), transversal representation of a crypt in which the Paneth cells are arranged in a radial pattern (marked by the dose boxes). The release of the antimicrobial grains (black dots, asterisk) in lumen is visible. Scale beams, 5 μm. ((D And One) Quantification of cup and paneth cells in the crypts. Results are obtained at 30 crypt per mouse (n = 1) and are displayed as average ± SD. One -way ANOVA P <0.0001; Post hoc by tukey's post -hoc test:*p <0.02, ** p <0.01, *** p <0.001 and **** p <0.0001.

Insights and implications

The study found that Alzheimer’s disease is associated with significant structural changes in the intestine. Advanced imaging revealed changes in the villi and crypts of the gut, which are crucial structures for the absorption of nutrients and immune response.

In mouse models of Alzheimer’s disease, the villi seemed elongated and the crypt seemed deeper compared to healthy checks, indicating disturbed intestinal architecture. Moreover, the intestinal epithelial barrier was considerably thinner, which, according to the researchers, could possibly endanger the protective functions of the intestine and increase permeability.

Moreover, the abundance of paneth and cup cells, which play roles in immune refuge and mucus secretion, was changed in particular into the Alzheimer’s models. An increase in these cells, along with increased mucus delivery, was also detected, which suggests a response to inflammatory conditions in the intestine. These findings correspond to earlier observations that intestinal disorders in Alzheimer’s disease can entail an inflammatory component.

The study also identified changes in the enteric nervous system, with changes in the neuron structure that may influence bowel motility and signaling on the brain. Moreover, morphology and the number of telocytes were changed, which suggests that limitations in intestinal recovery mechanisms.

In addition, the study found significant changes in Peyer’s patches and isolated lymphoid follicles, crucial for intestinal immune surveillance, indicating that Alzheimer’s disease can cause increased immune response in the intestine.

Conclusions

In general, the research showed that Alzheimer’s disease not only influences the brain, but also the structural integrity and the immune function of the intestine. This study emphasized the potential relationship between intestinal changes and Alzheimer’s disease and the importance of intestinal health in neurodegenerative disorders.

In addition, the researchers suggested that they could reveal these changes as early biomarkers of Alzheimer’s disease by structural changes and immune reactions in the gut. Insight into these intestinal brain interactions can lead to innovative treatments aimed at reducing the progression of Alzheimer’s, which further emphasizes the importance of holistic approaches in tackling complex neurological diseases.