The human master circadian clock is vulnerable to tau pathology in the early stages of Alzheimer’s: a postmortem neuropathology using spatial in‐situ proteomics
Our study sheds light on the previously unexplored molecular and pathological changes occurring in SCN during AD progression. The SCN is vulnerable to AD-tau pathology and show immune dysregulation even at Braak1 but protected against beta-amyloid accumulation. This vulnerability pattern in SCN supports the idea that SCN dysfunction contributes to circadian rhythm disturbances in AD, observed even in the stage before the onset of cognitive disorder. Furthermore, the preservation of SON, a neighboring nucleus with AVP neurons but not directly connected in a neuronal circuit with the SCN, corroborates that SCN is early vulnerable to AD. PVN neurons exhibited similar but milder pattern of protein dysregulation in the early stages to the SCN, implying the effect may be caused by the efferent projection from the SCN. These results open up opportunities for tailored interventions to alleviate circadian rhythm disruptions in AD.
Authors
- Lea T. Grinberg (ORCID: https://orcid.org/0000-0002-6809-0618)
- Renata Elaine Paraízo Leite (ORCID: https://orcid.org/0000-0002-5878-398X)
- Felipe Luiz Pereira (ORCID: https://orcid.org/0000-0001-9326-2365)
- Gowoon Son (ORCID: https://orcid.org/0000-0003-1173-2218)
- Wenhan Chang (ORCID: https://orcid.org/0000-0001-6583-7176)
- Carlos Augusto Pasqualucci (ORCID: https://orcid.org/0000-0001-6608-2473)
- Song Hua Li
- Salvatore Spina (ORCID: https://orcid.org/0000-0003-3570-9143)
- Chia‐Ling Tu (ORCID: https://orcid.org/0000-0002-7323-7733)
- Vítor Ribeiro Paes (ORCID: https://orcid.org/0000-0001-8752-5624)
- Thomas C. Neylan (ORCID: https://orcid.org/0000-0002-1572-2626)
- Cláudia Kimie Suemoto (ORCID: https://orcid.org/0000-0002-5942-4778)
- Mihovil Mladinov (ORCID: https://orcid.org/0000-0002-4886-7119)
- William W. Seeley (ORCID: https://orcid.org/0000-0003-1410-2027)
- Grace Judge
- Wilson Jacob Filho (ORCID: https://orcid.org/0000-0003-2290-4492)
Institutions
- San Francisco VA Medical Center (US)
- Universidade de São Paulo (BR)
- University of California, San Francisco (US)
- University Memory and Aging Center (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.088431
- Citations
- 3
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 0.82