Ezekiel, K. | Search bioRxiv

bioRxiv2026

Molecular and Structural Characterization Reveals Divergent Extracellular Vesicle Profiles Between Wild Type and Alzheimer's Disease Cerebrocortical Organoids

Alzheimers disease (AD) is a neurodegenerative disorder affecting millions of patients globally. Despite significant efforts from researchers in recent decades, there are still many unanswered questions about AD pathogenesis. AD patient brains manifest changes in extracellular vesicles (EVs) secreted from diseased neurons, and the effect of this phenomenon remains poorly understood. EVs contain a variety of biomolecules and play a critical role in cell-to-cell communication in all eukaryotic organisms. Here, we report a thorough characterization of small EVs purified from cultures of human cerebrocortical organoids. These organoids are differentiated from human patient-derived stem cells that bear a familial AD mutation in the presenilin 1 (PSEN1) gene, or from an isogenic wildtype (WT) control. The organoid conditioned media was aspirated from cultures and processed for EV enrichment using a non-invasive technique that requires no cellular disruption. EVs purified from AD organoid conditioned media have a wider size distribution and show differential expression of tetraspanins CD63, CD9, and CD81 when compared to WT organoid-derived EVs. AD organoid-derived EVs can have single, double, and even triple membranes and display luminal fibrillar material. A deep proteomic profiling of the EVs reveals several statistically significant differences, including evidence for modifications in secretory autophagy. EV isolates from both WT and AD organoids show strong binding to amyloid detecting dyes, both in bulk fluorescence and fluorescence microscopy assays. After a 1-week co-culture of AD organoids with WT organoids, there is evidence of endosomal membrane transfer between the isogenic cultures with an increase in amyloid-{beta} peptides in the WT organoids. These observations support the notion that non-cell-autonomous spread of amyloid-containing EVs in human AD brains can be modeled in a cerebral organoid system.

neuroscience↗

bioRxiv2025

Impact of Environmental Variables on the Seasonal Dynamics and Relative Abundance of Endosymbionts in Glossina Species in Northern Nigeria

This study explores how environmental factors influence the seasonal patterns and endosymbiont abundance in Glossina species across four ecological zones in northern Nigeria. Tsetse flies--the vectors of African trypanosomiasis--host both obligate and facultative endosymbionts, including Wigglesworthia glossinidia, Sodalis glossinidius, and Wolbachia pipientis, which affect their physiology and vector capacity. Over two years, 7,632 tsetse flies were collected and examined for species distribution, symbiont prevalence, and local climate variables (temperature, humidity, and vegetation index). Glossina tachinoides was most prevalent (55.78%), followed by G. morsitans submorsitans (29.36%) and G. palpalis palpalis (14.86%), each showing site-specific distribution. Endosymbiont prevalence rose markedly during the wet season (e.g., Yankari: 73.41% to 94.83%, p < 0.0001), especially for Sodalis, which declined under dry conditions. Strong negative correlations with temperature (r = -0.99, p = 0.0001) and positive correlations with humidity (r = +0.99, p = 0.0005) were observed. These patterns reflect the vulnerability of tsetse-symbiont systems to climate stress and underscore challenges for control strategies. Broad-area methods may suit G. tachinoides, while targeted trapping is more suitable for G. palpalis. The resilience of Wolbachia suggests its utility for paratransgenic control. The study emphasizes the importance of integrated, climate-aware surveillance and intervention strategies to mitigate trypanosomiasis risk. Author SummaryTsetse flies transmit African trypanosomiasis, a disease affecting livestock and rural livelihoods in sub-Saharan Africa. These flies harbor bacterial endosymbionts that influence their biology and vector competence. This study investigated how seasonal changes in temperature, humidity, and vegetation affect the abundance of tsetse flies and their symbionts in northern Nigeria. We found that certain symbionts, especially Sodalis glossinidius, decline sharply during hot-dry periods, while Wolbachia remains stable. Our findings highlight the need for adaptive, climate-informed vector control strategies and provide insights for integrating microbial monitoring into trypanosomiasis surveillance systems.

molecular biology↗