| Title: |
A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism |
| Authors: |
Flores Almazan, Victoria G; Laborc, Klaudia F; De Sanctis, Claudia; Thorn, Emma L; Goldstein, Adam; Cervera, Alessandra; Quintana Mora, Dalilah F; Mendez, Yolfrankcis; McGoldrick, Anya C; Chiu, Lily Yu-Chia; Hossain, Quazi I; McQuillan, Stephanie; Lind-Watson, Kourtni; Walker, Jamie M; Walker, Ruth H; Nirenberg, Melissa J; Crary, John F |
| Contributors: |
American Parkinson Disease Association; NIH |
| Source: |
Journal of Neuropathology & Experimental Neurology ; ISSN 0022-3069 1554-6578 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Neuropathologic features diagnostic of parkinsonian disorders infrequently occur in isolation; hyperphosphorylated tau (p-tau) and amyloid plaques are often observed in combination with α-synuclein deposition. Co-pathologies in neurodegenerative diseases are now recognized as the norm rather than an exception, but existing neuropathological assessment tools do not capture the complexity of concurrent co-pathologies. Characterization of this co-pathology is critical, as it has the potential to identify synergistic mechanisms. We developed a hierarchical cytoarchitectural classification system, which we applied to an autopsy series of military veterans with parkinsonism (n = 26), focusing on Lewy and neurofibrillary pathologies. We defined co-pathology as Type A (co-morbid), Type B (co-regional), Type C (co-cellular), or Type D (co-aggregate). The regional distributions of each co-pathology subtype were assessed using double-label immunohistochemistry in the frontal cortex, hippocampal formation, and midbrain. The frontal cortex demonstrated only subtypes A-C (no co-aggregates), whereas the midbrain and hippocampus showed all subtypes of copathology (A-D). In summary, we show marked differences in the prevalence and levels of mixed α-synuclein and tau pathology in this cohort. Our classification system has the potential to be applied broadly for the study of co-pathology in neurodegenerative disorders. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/jnen/nlaf137 |
| DOI: |
10.1093/jnen/nlaf137/66185247/nlaf137.pdf |
| Availability: |
https://doi.org/10.1093/jnen/nlaf137; https://academic.oup.com/jnen/advance-article-pdf/doi/10.1093/jnen/nlaf137/66185247/nlaf137.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.2D68024 |
| Database: |
BASE |