Pathological Interface between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies

U. Sengupta, M.J. Guerrero-Muñoz, D.L. Castillo-Carranza, C.A. Lasagna-Reeves, J.E. Gerson, A.A. Paulucci-Holthauzen, S. Krishnamurthy, M. Farhed, G.R. Jackson, R. Kayed

Resultado de la investigaciónrevisión exhaustiva

96 Citas (Scopus)

Resumen

Background Aberrant accumulation of α-synuclein constitutes inclusion bodies that are considered a characteristic feature of a group of neurological disorders described as synucleinopathies. Often, multiple disease-causing proteins overlap within a given disease pathology. An emerging body of research focuses on the oligomeric populations of various pathogenic proteins, considering them as the culprits causing neuronal damage and degeneration. To this end, the use of conformation-specific antibodies has proven to be an effective tool. Previous work from our laboratory and others has shown that oligomeric entities of α-synuclein and tau accumulate in their respective diseases, but their interrelationship at this higher order has yet to be shown in synucleinopathies. Methods Here, we used two novel conformation-specific antibodies, F8H7 and Syn33, which recognize α-synuclein oligomers and were developed in our laboratory. We investigated brain tissue from five of each Parkinson's disease and dementia with Lewy bodies patients by performing biophysical and biochemical assays using these antibodies, in addition to the previously characterized anti-tau oligomer antibody T22. Results We demonstrate that in addition to the deposition of oligomeric α-synuclein, tau oligomers accumulate in these diseased brains compared with control brains. Moreover, we observed that oligomers of tau and α-synuclein exist in the same aggregates, forming hybrid oligomers in these patients' brains. Conclusions In addition to the deposition of tau oligomers, our results also provide compelling evidence of co-occurrence of α-synuclein and tau into their most toxic forms, i.e., oligomers suggesting that these species interact and influence each other's aggregation via an interface in synucleinopathies.

Idioma originalEnglish
Páginas (desde-hasta)672-683
Número de páginas12
PublicaciónBiological Psychiatry
Volumen78
N.º10
DOI
EstadoPublished - 15 nov 2015
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Psiquiatría biológica

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