The role of the gut-brain axis in at-genetic-risk and clinical Alzheimer’s disease.

Dietrich, Celina (2021) The role of the gut-brain axis in at-genetic-risk and clinical Alzheimer’s disease. Doctoral thesis, University of East Anglia.

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Abstract

Introduction: The intestinal microbiome is emerging as an important modulator of health and disease. The Gut-Brain axis has been implicated in Alzheimer’s disease (AD) and is associated with intestinal dysbiosis. It is unknown if the Gut-Brain axis is involved in the preclinical course of AD. Understanding the role of the Gut-Brain axis in an at-genetic risk AD (APOε4 carriers) may provide a microbial signature that can aid diagnosis and intervention strategies.

Aims: To examine the role of the intestinal microbiome in AD development, I assessed APOε4 carriers and non-carriers neuropsychological, cardiovascular and brain integrity at baseline and longitudinally studied their intestinal microbiome at baseline, 6- and 12-months. Finally, the APOE findings were contrasted against a cohort of clinical AD patients.

Methods and Results: Baseline results showed that APOE groups did not differ on neuropsychological, cardiovascular and brain integrity measures, with the exception of LDL being elevated in the APOε4 carriers. The baseline measurements of the microbiome via whole-genome shotgun metagenomics highlighted ten differentially abundant taxa by genotype. Longitudinally, there was increased abundance of Prevotellaceae, Prevotella and Ruminococcus obeum in APOε4 carriers. Functionally, differences in 20 KEGG pathways existed, including changes in energy and nitrogen metabolism. Finally, shotgun metagenomics sequencing data, indicated that the intestinal microbiota of AD patients is characterized by large-scale and taxa-specific differences versus APOE groups, including reduced α-diversity, altered taxa abundances and changes in 63 metabolic pathways.

Conclusion: Despite APOE groups being well-matched for neuropsychological, cardiovascular and brain integrity measures, except LDL, numerous taxa and functional pathways differed between the APOE cohorts on a cross-sectional and longitudinal level. Although diversity and global compositional measures were not consistently different, this indicates that microbiota changes are already present in at-genetic-risk of AD people. In the AD patient group, there was reduced diversity, distinct compositional profiles and altered taxonomy and function indicating increased intestinal microbial dysbiosis.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Chris White
Date Deposited: 22 Mar 2022 13:41
Last Modified: 22 Mar 2022 13:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/84221
DOI:

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