@article{32c76e94460d47f3bfb4f8023c3180de,
title = "APOE ε2 is associated with increased tau pathology in primary tauopathy",
abstract = "Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer{\textquoteright}s disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy.",
author = "Na Zhao and Liu, {Chia Chen} and {Van Ingelgom}, {Alexandra J.} and Cynthia Linares and Aishe Kurti and Knight, {Joshua A.} and Heckman, {Michael G.} and Diehl, {Nancy N.} and Mitsuru Shinohara and Martens, {Yuka A.} and Attrebi, {Olivia N.} and Leonard Petrucelli and Fryer, {John D.} and Wszolek, {Zbigniew K.} and Graff-Radford, {Neill R.} and Caselli, {Richard J.} and Sanchez-Contreras, {Monica Y.} and Rosa Rademakers and Murray, {Melissa E.} and Shunsuke Koga and Dickson, {Dennis W.} and Ross, {Owen A.} and Guojun Bu",
note = "Funding Information: We thank P. Sullivan for developing and contributing the apoE-TR mice, and K. Jansen-West, E. Perkerson, and M. Davis for preparing AAV-TauP301L and AAV-GFP control viruses. We are grateful to L. Rousseau and M. Castanedes-Casey for helping with the preparation of mouse brain slices and immunohistochemical staining. This work was supported by NIH grants R01AG046205, R37AG027924, R01AG057181, R01AG035355, RF1AG051504, and P50AG016574 (to G.B.); R01NS078086 (to O.A.R.); and R35NS097261 (to R.R.); a grant from the Cure Alzheimer{\textquoteright}s Fund (to G.B.); Mayo Clinic Alzheimer{\textquoteright}s Disease Research Center (ADRC) (P50AG016574, to D.W.D., G.B. and N.Z.); BrightFocus Fellowship and Alzheimer{\textquoteright}s Association Research Grant (to C.-C.L.); Mayo Clinic Udall Center of Excellence (NINDS P50NS072187, to Z.K.W., R.R., D.W.D. and O.A.R.); NINDS Tau Center without Walls (U54-NS100693, to L.P., D.W.D., R.R. and O.A.R.); the Mayo Clinic Foundation and the Mayo Clinic Center for Individualized Medicine (to O.A.R.); Mayo Clinic Neuroscience Focused Research Team (to Z.K.W.). Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-06783-0",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}