Strickland, Michael R.
https://orcid.org/0000-0002-3899-5651
Mayo Clinic
Washington University in St. Louis
Citations 2
Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference
Kloske, Courtney M. , Blue, Elizabeth , Carrillo, María C. , Chen, Xiaoying , Chiba‐Falek, Ornit , Davis, Albert A. , Paolo, Gilbert Di , Garretti, Francesca , Golden, Lesley R. , Heinecke, Jay W. , Herz, Joachim, Huang, Yadong , Kanekiyo, Takahisa , Khvorova, Anastasia, Hertog, Sascha J. Koppes‐den, Lamb, Bruce T. , Lawler, Paige E. , Litvinchuk, Alexandra , Liu, Chia‐Chen , Michaelson, D. M., Miller, Justin J. , Morganti, Josh M. , Oosthoek, Marlies , Ramachandran, Kapil V. , Ramakrishnan, Abhirami , Robert, Aiko, Sexton, Claire E. , Shah, Nilomi, Shue, Francis , Strickland, Michael R. , TCW, Julia , Thierry, Manon, Tuckey, Ryan A. , Ulrich, Jason D. , Wang, Na , Weninger, Stacie, Zhao, Na , Goate, Alison , Liu, Chia-Chen , Shue, Francis , Zhao, Na , Goate, Alison M , Belloy, Michaël E. , Bowman, Gregory R. , Gate, David M , Iadecola, Costantino , Johnson, Lance A. , Karch, Celeste M. , Khvorova, Anastasia , Hertog, Sascha Koppes-den , Le Guen, Yann , Mahinrad, Simin , Marcora, Edoardo , Mariño, Claudia , Narayan, Priyanka , Naslavsky, Michel Satya , Raulin, Ana‐Caroline , Saleh, Rasha N.M. , Sible, Isabel J. , Soranno, Andrea , Tsai, Li‐Huei , Kant, Rik van der , Wellington, Cheryl L. , Yassine, Hussein N. , Bu, Guojun , Holtzman, David M.
Alzheimer's & Dementia | July 19, 2024 | Volume: 20 | Issue: 9 | Pages: 6590-6605
AbstractINTRODUCTIONThe apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid‐beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex‐dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.METHODSIn 2023, the Alzheimer's Association convened multidisciplinary researchers at the “AAIC Advancements: APOE” conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE‐targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function.RESULTSThis manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field.DISCUSSIONUnderstanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine.Highlights APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid‐beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.
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.