Reddy, Joseph
Mayo Clinic
From the Department of Neurology (P.W.T., G.S.D., O.P.F., N.E.-T., N.G.-R.), Department of Neuroscience (M.A., A.I.S.-B., Z.S.Q., J.S.R., N.E.-T., O.R.), Department of Neurosurgery (S.S.G., K.C.), Division of Clinical Trials and Biostatistics (C.T.B., M.G.
Citations 2
CWH43 Variants Are Associated With Disease Risk and Clinical Phenotypic Measures in Patients With Normal Pressure Hydrocephalus
Tipton, Philip W. , Atık, Merve, Soto‐Beasley, Alexandra I. , Day, Gregory S. , Chaichana, Kaisorn L. , Fermo, Olga , Ball, Colleen T. , White, Launia J. , Quicksall, Zachary , Reddy, Joseph S. , Elder, Benjamin D. , Ertekin‐Taner, Nilüfer , Ross, Owen A. , Graff‐Radford, Neill R. , Chaichana, Kaisorn, Fermo, Olga P, Reddy, Joseph , Ramanan, Vijay K , Ross, Owen A , Tipton, Philip W , Day, Gregory S , Beasley, Alexandra I , Grewal, Sanjeet S. , Heckman, Michael G. , Ramanan, Vijay K. , Vemuri, Prashanthi
Neurology Genetics | July 19, 2023 | Volume: 9 | Issue: 5 | Pages: No page available
TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer’s disease
Chakrabarty, Paramita , Li, Andrew, Ladd, Thomas B., Strickland, Michael R. , Koller, Emily J., Burgess, Jeremy D. , Funk, Cory C. , Allen, Mariet , Yaroshenko, Mariya, Wang, Xue , Younkin, Curtis, Reddy, Joseph S. , Lohrer, Benjamin , Mehrke, Leonie S. , Moore, Brenda D. , Ceballos‐Diaz, Carolina, Rosario, Awilda M., Medway, Christopher, Janus, Christopher, Li, Hongdong , Giasson, Benoit I. , Price, Nathan D. , Younkin, Steven G. , Ertekin‐Taner, Nilüfer , Golde, Todd E. , Reddy, Joseph , Mehrke, Leonie, Price, Nathan D , Golde, Todd E , Cruz, Pedro E. , Wang, Xue, Liu, Xuefei , Li, Hong-Dong, Dickson, Dennis W.
Journal of Experimental Medicine | August 29, 2018 | Volume: 215 | Issue: 9 | Pages: 2247-2264
There is considerable interest in harnessing innate immunity to treat Alzheimer’s disease (AD). Here, we explore whether a decoy receptor strategy using the ectodomain of select TLRs has therapeutic potential in AD. AAV-mediated expression of human TLR5 ectodomain (sTLR5) alone or fused to human IgG4 Fc (sTLR5Fc) results in robust attenuation of amyloid β (Aβ) accumulation in a mouse model of Alzheimer-type Aβ pathology. sTLR5Fc binds to oligomeric and fibrillar Aβ with high affinity, forms complexes with Aβ, and blocks Aβ toxicity. Oligomeric and fibrillar Aβ modulates flagellin-mediated activation of human TLR5 but does not, by itself, activate TLR5 signaling. Genetic analysis shows that rare protein coding variants in human TLR5 may be associated with a reduced risk of AD. Further, transcriptome analysis shows altered TLR gene expression in human AD. Collectively, our data suggest that TLR5 decoy receptor–based biologics represent a novel and safe Aβ-selective class of biotherapy in AD.