Human Palatine Tonsils Are Linked to Alzheimer’s Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection

Abstract

Amyloid-β (Aβ)-peptide production or deposition in the neuropathology of Alzheimer’s disease (AD) was shown to be caused by chronic inflammation that may be induced by infection, but the role of pathogenic-bacteria-related AD-associated Aβ is not yet clearly understood. In this study, we validated the hypothesis that there is a correlation between the Aβ-protein road and bacterial infection and that there are effects of bacteria, Staphylococcus aureus (S. aureus), on the Aβ road in the inflammatory environment of human tonsils. Here, we detected Aβ-peptide deposits in human tonsil tissue as well as tissue similar to tonsilloliths found in the olfactory cleft. Interestingly, we demonstrated for the first time the presence of Staphylococcus aureus (S. aureus) clustered around or embedded in the Aβ deposits. Notably, we showed that treatment with S. aureus upregulated the Aβ-protein road in cultures of human tonsil organoids and brain organoids, showing the new role of S. aureus in Aβ-protein aggregation. These findings suggest that a reservoir of Aβ and pathogenic bacteria may be a possible therapeutic target in human tonsils, supporting the treatment of antibiotics to prevent the deposition of Aβ peptides via the removal of pathogens in the intervention of AD pathogenesis.

Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes

“…For example, TREM2 itself is expressed by lymph node subcapsular macrophages 21 and both Aβ and phosphorylated tau can be found in the periphery including the head and neck. [22][23][24] Nonetheless, as exemplified by a study of post-stroke tonsillar biopsies, these regions themselves can be differentially enriched for drained brain-derived proteins. 25 Moreover, as several independent animal models have shown, both dynamically and at post-mortem, the CLNs receive CSF brain drainage from the meningeal lymphatics.…”

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics

“…Organoids represent another promising approach for in vitro studies of sepsis. These miniature 3D organ-like structures are developed by culturing organ-specific cells, such as intestinal tissue ( Siwczak et al., 2021 ), lung tissue ( Bosáková et al., 2022 ), or brain tissue ( Lim et al., 2022 ) under conditions that promote self-organization and differentiation. Recent advancements have allowed researchers to create lung, liver, and intestinal organoids to mimic in vivo inflammation more realistically.…”

“…Recent advancements have allowed researchers to create lung, liver, and intestinal organoids to mimic in vivo inflammation more realistically. These models provide valuable insights into the tissue-specific molecular responses during inflammatory conditions ( Lim et al., 2022 ), including the dysregulation of tight junction proteins, altered metabolic pathways and the release of proinflammatory cytokines ( Lee et al., 2014 ). However, organoids, too, have their limitations.…”

Benefit and safety of antibiotics for Alzheimer’s disease: Protocol for a systematic review and meta-analysis

“…Staphylococcus aureus infection can upregulate Aβ expression and aggregation in human tonsils and olfactory fissures, and S. aureus aggregates around or is embedded in Aβ deposits. [21] Studies have found that pathogenic microorganisms can directly invade the brain through various pathways, such as the damaged blood-brain barrier, oral cavity, trigeminal nerve, and olfactory system. [8,[22][23][24] Aβ peptides are protein fragments released after the cleavage of amyloid precursor protein on the cell membrane (e.g., neurons).…”