Introduction: Alzheimer’s disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-b (Ab) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG1-Fc. Methods: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. Results: NPT088-lowered Ab plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. Discussion: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Ab and tau, the hallmark pathologies of AD.
Alzheimer's and Dementia: Translational Research and Clinical Interventions
Digital Object Identifier (DOI)
Levenson, Jonathan M.; Schroeter, Sally; Carroll, Jenna C.; Cullen, Valerie; Asp, Eva; Proschitsky, Ming; Chung, Charlotte H.Y.; Gilead, Sharon; Nadeem, Muhammad; Dodiya, Hemraj B.; Shoaga, Shadiyat; Mufson, Elliott J.; Tsubery, Haim; Krishnan, Rajaraman; Wright, Jason; Solomon, Beka; Fisher, Richard; and Gannon, Kimberley S., "NPT088 reduces both amyloid-b and tau pathologies in transgenic mice" (2016). Translational Neuroscience. 339.