IgA biome impacts memory and immune cell profiles in a mouse model of Alzheimer's disease

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B116
Abstract ID: 5341

Presenting Author:
Suba Nookala , Assistant Professor at Univ. of North Dakota Sch. of Med. and Hlth. Sci.

Abstract:

Altered gut bacteria (dysbiosis) have been implicated as causative in Alzheimer’s disease (AD). We hypothesized that pathogenic bacteria in the dysbiotic profile seen in AD could be identified via IgA coating (IgA biome). Using a well-established AppNL-G-F mouse model of AD, our data show that female AppNL-G-F mice showed a significantly higher percentage of fecal IgA biome compared to wild-type C57Bl6/J (WT) female mice (P<0.01). To identify the IgA biome in the female mice, fecal pellets from female AppNL-G-F and WT mice were analyzed by 16s rRNA seq of IgA-sorted bacteria (IgA-seq). At the family level, operational taxonomic units of Burkholderiaceae, Streptococcaceae, Prevotellaceae, Erysipelotrichaceae, and Paenibacillaceae were among the most abundant in AppNL-G-F mice. In stark contrast, the commensal and beneficial bacteria of the family Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae were abundant in the WT mice. Behavior data from the novel object recognition test demonstrated that cross-sex presentation of female AppNL-G-F  IgA biome to bowel-cleansed male AppNL-G-F and WT mice significantly reduced recognition memory in WT males, that correlated with decreased circulating levels of MHC-II (P<0.01), CD19 (P<0.05)  and CD45 (P<0.01) expressing cells. Our data provide a new understanding of the IgA biome as a contributor to sex-specific behavior and immune subset changes in AD. Identification of key bacterial species may reveal novel therapeutic strategies.