Open Accessα-Synuclein modulates tau spreading in mouse brains
Author(s) -
Fares Bassil,
Emily S. Meymand,
Hannah J. Brown,
Hong Xu,
Timothy Cox,
Shankar Pattabhiraman,
Chantal Maghames,
Qihui Wu,
Bin Zhang,
John Q. Trojanowski,
Virginia M.Y. Lee
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20192193
Subject(s) - tau pathology , in vivo , tau protein , in vitro , microbiology and biotechnology , neuroscience , fibril , parkinson's disease , biology , alpha synuclein , genetically modified mouse , endogeny , alzheimer's disease , chemistry , transgene , pathology , biophysics , disease , medicine , biochemistry , genetics , gene
α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson’s disease (PD) and Alzheimer’s disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate–derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients.