Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease.

Microbial communities in the intestinal tract are suggested to impact the ethiopathogenesis of Alzheimer's disease (AD). The human microbiome might modulate neuroinflammatory processes and contribute to neurodegeneration in AD. However, the microbial compositions in patients with AD at different stages of the disease are still not fully characterized. We used 16S rRNA analyses to investigate the oral and fecal microbiota in patients with AD and mild cognitive impairment (MCI; n = 84), at-risk individuals (APOE4 carriers; n = 17), and healthy controls (n = 50) and investigated the relationship of microbial communities and disease-specific markers via multivariate- and network-based approaches. We found a slightly decreased diversity in the fecal microbiota of patients with AD (average Chao1 diversity for AD = 212 [SD = 66]; for controls = 215 [SD = 55]) and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, and Porphyromonadaceae. The diversity in the oral microbiota was increased in patients with AD and at-risk individuals (average Chao1 diversity for AD = 174 [SD = 60], for at-risk group = 195 [SD = 49]). Gram-negative proinflammatory bacteria including Haemophilus, Neisseria, Actinobacillus, and Porphyromonas were dominant oral bacteria in patients with AD and MCI and the abundance correlated with the cerebrospinal fluid biomarker. Taken together, we observed a strong shift in the fecal and the oral communities of patients with AD already prominent in prodromal and, in case of the oral microbiota, in at-risk stages. This indicates stage-dependent alterations in oral and fecal microbiota in AD which may contribute to the pathogenesis via a facilitated intestinal and systemic inflammation leading to neuroinflammation and neurodegeneration.

Hippocampal Dentate Gyrus Atrophy Predicts Pattern Separation Impairment in Patients with LGI1 Encephalitis.

Day-to-day life involves the perception of events that resemble one another. For the sufficient encoding and correct retrieval of similar information, the hippocampus provides two essential cognitive processes. Pattern separation refers to the differentiation of similar input information, whereas pattern completion reactivates memory representations based on noisy or degraded stimuli. It has been shown that pattern separation specifically relies on the hippocampal dentate gyrus (DG), whereas pattern completion is performed within CA3 networks. Lesions to these hippocampal networks emerging in the course of neurological disorders may thus affect both processes. In anti-leucine-rich, glioma-inactivated 1 (LGI1) encephalitis it has been shown in animal models and human imaging studies that hippocampal DG and CA3 are preferentially involved in the pathophysiology process. Thus, in order to elucidate the structure-function relationship and contribution of hippocampal subfields to pattern separation, we examined patients (n = 15, age range: 36-77 years) with the rare LGI1 encephalitis showing lesions to hippocampal subfields. Patients were tested 3.53 ±â€¯0.65 years after the acute phase of the disease. Structural sequelae were determined by hippocampal subfield volumetry for the DG, CA1, and CA2/3. Patients showed an overall memory deficit including a significant reduction in pattern separation performance (p = 0.016). In volumetry, we found a global hippocampal volume reduction. The deficits in pattern separation performance were best predicted by the DG (p = 0.029), whereas CA1 was highly predictive of recognition memory deficits (p < 0.001). These results corroborate the framework of a regional specialization of hippocampal functions involved in cognitive processing.