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Intravenous immunoglobulin reduces tau pathology and preserves neuroplastic gene expression in the 3xTg mouse model of Alzheimer's disease

Bibliographic

Year of Publication:
2014
Contact PI Name:
Scott E. Counts
Contact PI Affiliation:
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA
Co-Authors:
S.E. Perez, B. He, E.J. Mufson
Primary Reference (PubMED ID):
Funding Source:
Baxter Biosciences
Study Goal and Principal Findings:

This study aimed at testing the extent to which IVIG (Gammagard) alters expression of NFT tau epitopes with the CA1 pyramidal neurons of the 3xTg AD mouse model. In addition to evaluating the effects of IVIG therapy on NFT pathology, the authors also compared gene expression profiles of plasma isolated from placebo and IVIG-treated 3xTg mice to identify putative mechanistic markers for the pathogenic events underlying both disease progression and therapeutic modification  by IVIG. The results show that IVIG abrogates the age dependent hippocampal tau pathological burden observed in the 3xTg mouse model of AD. Moreover, the gene expression profiling experiments revealed that IVIG may slow tangle propagation by stabilizing or increasing cytoskeletal and calcium signaling plasticity and phosphorylation-based cellular homeostatic mechanisms in the face of mounting AD pathology in these mice. The data presented suggest that IVIG is a useful tool for understanding the mechanisms of NFT formation and prevention that will aid in the further design of IVIG clinical trials for the treatment of AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Gammagard
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1xTau
Strain/Genetic Background:
Not Reported

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
Biomarkers
Dose
Formulation
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

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
Neurofibrillary Tau Tangles
beta Amyloid Load
Activated Astrocytes
Biochemical
Total Tau Protein
Omics
Micro Array Expression Analysis
Immunochemistry
Intracellular beta Amyloid Peptide
Activated Astrocytes
Immunology
IgG Antibody Titers