Biology subjects

Ngouongo, Y. W.

Publications and source records attributed to Ngouongo, Y. W..

3 recordsLinked to original sources

bioRxiv2025

Altered Gut Microbiota Mediates the Association between APOE Genotype and Amyloid-β Accumulation in Middle-Aged Adults

ImportanceThe apolipoprotein E (APOE) {varepsilon}4 allele is the strongest genetic risk factor for Alzheimers disease (AD), yet the mechanisms linking APOE to amyloid-{beta} (A{beta}) pathology remain incompletely understood. Emerging evidence suggests that the gut microbiome may modulate neurodegeneration; however, its role as a mediator in the APOE-A{beta} relationship remains unclear. ObjectiveTo evaluate whether specific microbial taxa mediate APOE-related effects on brain A{beta} burden in an established population-based study of middle-aged adults. Design, Setting, and ParticipantsThis cross-sectional study analyzed data from the Framingham Heart Study cohort. Data were collected at the third examination visit (n = 227, %Female = 58, mean age = 56.5 {+/-} 8.3), between 2016 and 2019. ExposuresGut bacterial DNA was sequenced using 16S rRNA, and amplicon sequence variants (ASVs) were agglomerated at various taxonomic levels (14 phyla, 70 families, and [~]140 genera). APOE genotypes were derived from blood DNA using PCR and restriction isotyping. Predicted microbial functional potential was based on KEGG Orthologs. Main Outcomes and MeasuresOverall and regional measures of cerebral amyloid-{beta} deposition were assessed using carbon-11 Pittsburgh (PiB) Compound-B PET scans. The global PiB deposition served as the primary outcome for "overall" amyloid burden. Regional amyloid deposition values were analyzed as secondary outcomes. ResultsA higher A{beta} burden was significantly associated with the depletion of protective genera (e.g., Faecalibacterium {beta} [95%CI],-0.35 [-0.40,-0.30]; Ruminococcus-0.25 [-0.27,-0.23]; Butyricicoccus-0.27 [-0.32,-0.22]) and the enrichment of pro-inflammatory taxa (e.g., Alistipes 0.07 [0.06, 0.08], Bacteroides 0.10 [0.07, 0.13]) and Barnesiella (0.18 [0.16, 0.20]). These associations were more pronounced in APOE {varepsilon}4 carriers, who exhibited a broader spectrum of microbial dysbiosis. Mediation analysis showed that Ruminococcus, Butyricicoccus, Clostridium, and Christensenellaceae collectively mediated [~]0.3-0.4% of the effect of APOE {varepsilon}4 on global A{beta} burden. Functional profiling revealed a reduced abundance of microbial genes involved in key metabolic pathways among individuals with higher A{beta} levels. Conclusion and RelevanceGut microbiome composition partially mediates the relationship between APOE {varepsilon}4 and cerebral amyloid burden. These findings support a gut-brain axis mechanism in AD and suggest that microbiome-targeted interventions may mitigate APOE-related risk.

neuroscience↗

bioRxiv2022

A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia

Dementia is multifactorial with Alzheimer (AD) and vascular (VaD) pathologies making the largest contributions. Genome-wide association studies (GWAS) have identified over 70 genetic risk loci for AD but the genomic determinants of other dementias, including VaD remain understudied. We hypothesize that common forms of dementia will share genetic risk factors and conducted the largest GWAS to date of "all-cause dementia" (ACD) and examined the genetic overlap with VaD. Our dataset includes 809,299 individuals from European, African, Asian, and Hispanic ancestries with 46,902 and 8,702 cases of ACD and VaD, respectively. We replicated known AD loci at genome-wide significance for both ACD and VaD and conducted bioinformatic analyses to prioritize genes that are likely functionally relevant, and shared with closely related traits and risk factors. For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and MRI markers of small vessel disease (HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). Our study identified genetic risks underlying all-cause dementia, demonstrating overlap with neurodegenerative processes, vascular risk factors (Type-II diabetes, blood pressure, lipid) and cerebral small vessel disease. These novel insights could lead to new prevention and treatment strategies for all dementias.

genetics↗

bioRxiv2022

Cerebral Small Vessel Disease Burden is Associated with Decreased Abundance of Gut Barnesiella intestinihominis Bacterium in the Framingham Heart Study

A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimers disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p-values < 0.001), as well as better executive function (p-values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and {beta}-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

neuroscience↗