Uncovering Etiological Roles in the Development of Alzheimer’s Disease (AD)
Friday, August 8, 2025
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
Uncovering Etiological Roles in the Development of Alzheimer’s Disease (AD)
Speaker:
Michiko Thwe, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Garth Ehrlich, PhD, FAAAS, FAAM
Professor
Department of Microbiology and Immunology
Department of Otolaryngology
College of Medicine
Drexel University
Details:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Despite decades of research, no effective therapy exists to prevent or halt its progression. Emergent findings have led to the recognition that there is a brain microbiota comprised of a complex community of microorganisms, including bacteria, fungi, and parasites that reside in the brain tissue and multiple studies have linked microbes and their biofilms with neurological, neurosurgical conditions, all indicating that the brain is not a sterile site. Moreover, alterations in this brain microbiota, leading to an AD pathobiome, likely play an etiological role in AD. Our preliminary findings, using pan-domain, species-specific, full-length 16S rRNA gene-based assay, identified distinct polymicrobial profiles in postmortem brain tissues of AD patients compared to age-matched controls (AMC). Notably, a Cutibacterium acnes (C. acnes)- and Methylobacterium-dominated consortium was enriched in AD samples, while Comamonas species were associated with normal aging brains. The various microbiome’s spatial distributions suggested a progressive large-scale failure of one or more of the brain’s networks, (vascular, lymphatic, or nervous), eventually leading to the AD-associated microbiome. specimens. The variance in sample abundances of the most prevalent bacterial species indicates they may interact synergistically, leading to increased pathology. These microbial communities exhibited spatial heterogeneity across brain regions, suggesting disruption of neurovascular or neuroimmune barriers may facilitate colonization.
The overarching goal of this study is to investigate the potential etiological and exacerbatory roles of non-viral microbial communities in AD pathogenesis. With the goal of obtaining a more complete picture of the microbial impact and interactions in the AD brain, the following specific aims address: 1), establishing protocols for spatial sampling and validate the authenticity of microbial signals by distinguishing true brain microbiota from contaminants in postmortem tissues; 2) applying these validated assays to map microbial diversity and structure across multiple brain regions from three neuro brain banks, enabling comparative analysis of microbial signatures and regional enrichment patterns, with a particular focus on C. acnes prevalence; and 3) utilizing comparative genomics and pan-genome analysis to assess the strain-level diversity and virulence potential of C. acnes, identifying genes and features that may underlie its role in neuroinflammation and tissue invasion.
Together, these aims will provide unprecedented insights into the spatial organization, strain-level diversity, and potential pathological roles of brain-resident microbes in Alzheimer’s disease, offering a new microbial dimension to AD research and opening avenues for novel diagnostic and therapeutic strategies.
Contact Information
Natalia Broz
njb33@drexel.edu