The Role of Apolipoprotein E4 Allele in the Gut Microbiome of Puerto Ricans with Alzheimer’s Disease

Gerianne Olivieri‐Henry,Javier A Ruiz‐Adames,Carlos Herrero‐Rivera,Vanessa Sepulveda,Fabián J Pérez‐Luzunaris,Michel Santiago‐Berríos,Ana Cecilia Sala‐Morales,Filipa Godoy‐Vitorino,Cecilia Michelle Soler‐Llompart

doi:10.1002/alz.083054

Gerianne Olivieri‐Henry, Javier A Ruiz‐Adames + Show 7 more

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AbstractBackgroundAlzheimer’s disease (AD) causes dementia, a debilitating disorder that gradually declines mental function and ends with death. Evidence suggests that the apolipoprotein E (ApoE) gene influences Alzheimer’s risk. Allele E2 is neuroprotective, E3 is neutral, and E4 is associated with a higher genetic risk for AD. Our main goal was to study the gut microbiome of Puerto Ricans with AD compared to unimpaired cognitive controls and its association with ApoE allele variants. We hypothesized that people with AD and does with less protective alleles have reduced microbial diversity.MethodsWe present the preliminary results of forty eight participants (n = 48), 24 with AD and 24 controls, with clinical and cognitive assessments. Fecal samples were collected for genomic DNA extractions followed by 16S rRNA genes (V4 region) amplification and ApoE genotyping was done at the PR‐INBRE CRI genomics core, using real‐time PCR TaqMan‐BHQ probes.ResultsControls, even with a single E4 allele, showed higher abundance of Ruminococcus bicirculans, absent in AD patients. Clostridium leptum was in higher abundance in controls with neuroprotective alleles E2E3 and in considerably reduced abundance in AD patient with E3E4 phenotype. Methanobrevibacter was in higher abundance in participants with any E4 allele than those with either E2 or E3 alleles. Faecalibacterium and Bacteroides were in higher abundance in controls compared to AD patients. Faecalibacterium, Ruminococcus, Clostridium and Bacteroides are anti‐inflammatory taxa and butyrate producers. Methanobrevibacter could favor metabolizing acetate to methane and thus antagonize the health‐directed butyrate benefits.ConclusionParticipants with any ApoE E4 allele have decreasing butyrate‐producing gut bacteria. This developing study area may open the possibility for preventive microbiome‐based therapies that could result in a clinical benefit for patients with and without AD.

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