Alzheimer's disease (AD) stands as a neurodegenerative disorder causing cognitive decline, posing a significant health concern for the elderly population in China. This study explored the effects of outer membrane vesicles (OMVs) from the gut microbiota of AD patients on learning and memory abilities and Tau protein phosphorylation in mice. In contrast to the OMVs from healthy controls and the PBS treatment group, mice treated with AD-OMVs exhibited notable declines in learning and memory capabilities, as evidenced by results from the Morris water maze, Y-maze, and novel object recognition tests. Immunohistochemistry and Western blot assessments unveiled elevated levels of hyperphosphorylated Tau in the cortex and hippocampus of mice treated with AD-OMVs. However, there were no alterations observed in the total Tau levels. In addition, AD-OMVs treated mice showed increased neuroinflammation indicated by elevated astrocytes and microglia. Molecular mechanism studies demonstrated that AD-OMVs could activate GSK3β, CDK5-Calpain and NF-κB pathways in mice hippocampus. These studies suggest AD patient gut microbiota derived OMVs can promote host Tau phosphorylation and improved neuroinflammation.

Objective. Neurodegenerative disease is a common neurodegenerative disorder. Lactobacillus pentosus (L. pentosus) plays a neuron-protective role. This study aimed to investigate the effects of L. pentosus on neurodegenerative diseases. Methods. Cells were treated with lipopolysaccharide (LPS) to establish neurodegenerative diseases model in vivo and with L. pentosus strain S-PT84. Reverse transcription-quantitative PCR (RT-qPCR) was applied to determine mRNA levels. Western blot was performed to detect protein expression. Cellular behaviors were detected using Cell Counting Kit-8 (CCK-8), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The interaction between baculoviral IAP repeat containing 3 (BIRC3) and NLR family CARD domain containing 4 (NLRC4) was predicted by STING and verified by western blot. Result. L. pentosus suppressed LPS-induced pyroptosis and promoted the cell viability of neurons. Additionally, L. pentosus suppressed the release of proinflammatory cytokines (interleukin 1 beta (IL-1β) and IL-18) and the protein expression of pyroptosis biomarkers (cleaved caspase1 (CL-CASP1) and N-terminal fragment gasdermin D (GSDMD-N)). Moreover, L. pentosus upregulated BIRC3, which induced the inactivation of NLRC4. However, BIRC3 knockdown alleviated the effects of L. pentosus and induced neuronal degeneration. Conclusion. L. pentosus may play a neuron-protective role via regulating BIRC3/NLRC4 signaling pathways. Therefore, L. pentosus may be a promising strategy for neurodegenerative diseases.

Background In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are associated with cognitive impairment. At the Fazekas visual scale, whether periventricular (PV) and deep (DW) components carry distinguishable information, and how much of the association is independent of education, remain unclear. Methods In 199 consecutive patients with CSVD imaging markers (2024–2025), 112 completed the Montreal Cognitive Assessment (MoCA). The primary analysis was a prespecified linear model of MoCA score on Fazekas score, age and education. Secondary analyses comprised component contrasts, competing models with minimum detectable effects (MDE), tests of non-linearity, and domain analyses with false discovery rate (FDR) control under three specifications. Results Fazekas score was independently associated with MoCA (β = −0.75, 95% CI − 1.23 to − 0.28; P = 0.002). PV and DW were each associated alone (− 1.76 and − 1.09) but did not differ ( P = 0.13); the minimum detectable DW effect equalled the PV estimate. Microbleeds and circulating markers showed no independent association. Severe grades scored 3.70 points lower ( P < 0.001), but categorical and linear models did not differ ( P = 0.08). Visuospatial and orientation domains met the FDR threshold in all three specifications; language was inconsistent. Education explained more variance than WMH (R² 0.24 versus 0.05) and added little to discrimination (area under the curve 0.74 to 0.75). Conclusions WMH burden was independently but modestly associated with cognition; component specificity was not resolvable and education was the dominant correlate. Fazekas grading should inform follow-up intensity rather than decide who needs assessment.