Human Palatine Tonsils Are Linked to Alzheimer’s Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection
Jung Yeon Lim,
Jung Eun Lee,
Han Kyung Kim,
Yeon-Joon Park,
Jung Ho Jeon,
Soon-A. Park,
Naeun Lee,
Il Hwan Lee,
Do Hyun Kim,
Seung Ho Yang,
Jongman Yoo,
Sung Won Kim
Affiliations
Jung Yeon Lim
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Jung Eun Lee
Department of Neurosurgery, St. Vincent Hospital, The Catholic University of Korea, Suwon 16247, Korea
Han Kyung Kim
Department of Microbiology, CHA University School of Medicine, Seongnam 13415, Korea
Yeon-Joon Park
Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Jung Ho Jeon
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Soon-A. Park
Department of Neurosurgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
Naeun Lee
Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul 06591, Korea
Il Hwan Lee
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Do Hyun Kim
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
Seung Ho Yang
Department of Neurosurgery, St. Vincent Hospital, The Catholic University of Korea, Suwon 16247, Korea
Jongman Yoo
Department of Microbiology, CHA University School of Medicine, Seongnam 13415, Korea
Sung Won Kim
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
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 load and bacterial infection and that there are effects of bacteria, Staphylococcus aureus (S. aureus), on the Aβ load 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 load 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.
