Alzheimer's disease is a progressive, neurodegenerative disorder that develops within the limbic system, spreading radially into anatomically linked brain association areas as the disease progresses. Analysis of temporal-lobe association of neocortex-derived extracellular fluid and cerebrospinal fluid from Alzheimer's disease patients shows an abundant presence of micro-RNA (miRNA), including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly sensitive LED-Northern dot-blot focusing technique, we detected the secretion of potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155 was found to induce Alzheimer-type gene expression changes in control brain cells. These included downregulation in the expression of an important repressor of the innate immune response, complement factor H (CFH). These effects were neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may provide a novel and efficacious treatment to stem the miRNA-mediated spreading of inflammatory signaling involved in Alzheimer's disease.
aDepartment of Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, Los Angeles
bDepartment of Surgery and Center for Translational Injury Research, University of Texas Health Science Center, Houston, Texas, USA
cRussian Academy of Medical Sciences, Moscow, Russia
Correspondence to Walter J. Lukiw, BS, MS, PhD, Department of Ophthalmology, LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA 70112-2272, USA Tel: +1 504 599 0842; fax: +1 504 568 5801; e-mail: email@example.com
Received March 29, 2012
accepted April 25, 2012