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Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats. | LitMetric

AI Article Synopsis

  • Alzheimer's disease (AD) affects not just cognition but also the gut microbiome (GMB) and metabolism, which can impact overall quality of life.
  • In a study with aged female TgF344-AD and wildtype rats, researchers assessed cognitive performance and analyzed gut microbiome composition across different intestinal regions.
  • Findings showed that TgF344-AD rats had significant cognitive impairments and specific GMB alterations linked to important metabolic functions, suggesting that gut health could play a role in AD treatment strategies.

Article Abstract

Alzheimer's disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179252PMC
http://dx.doi.org/10.1016/j.nbas.2024.100119DOI Listing

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