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Passive immunization in JNPL3 transgenic mice using an array of phospho-tau specific antibodies


Year of Publication:
Contact PI Name:
Peter Davies
Contact PI Affiliation:
Litwin-Zucker Center for Research in Alzheimer's Disease, Feinstein Institute for Medical Research, North Shore/LIJ Health System, Manhasset, New York, USA
Cristina d’Abramo, Christopher M. Acker, Heidy Jimenez
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

The purpose of this study was to test the efficacy of specific phospho-tau monoclonal antibodies-[CP13 (pSer202), RZ3 (pThr231) and PG5 (pSer409)] for efficacy in preventing and clearing tau pathology in the JNPL3 transgenic mouse model of tauopathy. The monoclonal antibodies used included two different phospho-tau Abs targeting phosphorylations appearing on tau from both normal adult brain and PHF-tau,CP13 (pSer202), RZ3 (pThr231), plus a phospho-tau Ab directed specifically to PHF-tau, PG5 (pSer409). As expected not all the antibodies exhibited the ability of reducing tau pathology. In fact, only CP13 was able to lower insoluble or soluble tau accumulation and tau phosphorylation in cortex and hindbrain. It is important to note that treatment with  PG5 caused a general remarkable accumulation of soluble and insoluble tau levels in the cortex and hippocampus. The author concluded that while some generalizations may now be possible about which tau epitopes to target, there is a real need to examine multiple different mouse models and examine dose-response relationships for antibodies that appear efficacious.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
CP13 (anti-Tau pSer202 Mab)
Therapeutic Target:
Tau Protein
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
RZ3 (anti-Tau pThr231 Mab)
Therapeutic Target:
Tau Protein
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
PG5 (anti-Tau pSer409 Mab)
Therapeutic Target:
Tau Protein

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
C57BL/6, DBA/2, SW Mixed Background
Animal Model Notes:
JNPL3 homozygous transgenic animals were purchased from Taconic. Cohorts of female JNPL3 were used as a model of hyperphosphorylation and aggregation of tau protein. This transgenic line expresses human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter and develops neurofibrillary tangles in an age and gene–dose dependent manner, as early as 4.5 months.

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Insoluble Tau
Soluble Tau
Aggregated Tau
Tau Protein