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Reductions in Aβ-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation


Year of Publication:
Contact PI Name:
Kim N. Green
Contact PI Affiliation:
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine California, USA
Anna Parachikova, Vitaly Visilevko, David H. Cribbs, Frank M. LaFerla
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
Study Goal and Principal Findings:

Multiple studies have shown that minocycline, a second-generation derivative of tetracycline, is neuroprotective in animal models of central nervous system injury and neurodegenerative diseases. These neuroprotective effects appear to be distinct from the antimicrobial activity of minocycline, but appear to be associated with the ability of minocycline to suppress p38 mitogen-activated protein kinase activity in microglia. Indeed, this minocycline-mediated suppression of p38, in both microglia and other cell types, appears to confer protection in a number of insult models. Previously minocycline has been shown to protect against Aβ-induced neuronal loss in the rat hippocampus, prevent hippocampal long-term potentiation (LTP) deficits induced by Aβ, reduce aggregation of Aβ into fibrils, and improve cognitive deficits in mouse models of AD, and in Aβ infused rats.

In this study the authors investigated the efficacy of minocycline on the AD-like pathology induced inflammation and cognitive decline observed in the 3xTg mouse model of AD. Results showed that minocycline treatment in this model prevents cognitive decline associated with beta amyloid and tau pathologies, reverses the inflammatory response to levels observed in non transgenic littermates, reduces insoluble and fibrillar Aβ, and exhibits differential effects on phosphorylation of tau despite reductions in p25.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:

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
Novel Object Recognition Test (NORT)
Morris Water Maze
Inhibitory Avoidance Test
beta Amyloid Load
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Brain-beta Amyloid Oligomers
Brain-beta Amyloid Fibrils
Amyloid Precursor Protein (APP) Metabolites
p25/p35/Cyclin-Dependent Kinase 5 Regulatory Subunit 1 (CDK5R1)
Proinflammatory Markers
Glial Fibrillary Acidic Protein (GFAP)
Activated Microglia
Activated Astrocytes