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Memantine leads to behavioral improvement and amyloid reduction in Alzheimer's-disease-model transgenic mice shown as by micromagnetic resonance imaging


Year of Publication:
Contact PI Name:
Thomas Wisniewski
Contact PI Affiliation:
Department of Neurology, New York University School of Medicine, New York, New York, USA
Henrieta Scholtzova, Youssef Z. Wadghiri, Moustafa Douadi, Einar M. Sigurdsson, Yong-Sheng Li, David Quartermain, Pradeep Banerjee
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Forest Research Institute
Study Goal and Principal Findings:

Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to improve learning and memory in several preclinical models of Alzheimer's disease (AD). Memantine has also been shown to reduce the levels of amyloid beta (A beta) peptides in human neuroblastoma cells as well as to inhibit A beta oligomer-induced synaptic loss. In this study, was assessed whether NMDA receptor inhibition by memantine in transgenic mice expressing human amyloid-beta precursor protein (APP) and presenilin 1 (PS1) is associated with cognitive benefit and amyloid burden reduction by using object recognition, micromagnetic resonance imaging (micro MRI), and histology. APP/PS1 Tg mice were treated either with memantine or with vehicle for a period of 4 months starting at 3 months of age. After treatment, the mice were subjected to an object recognition test and analyzed by ex vivo micro MRI, and histological examination of amyloid burden. micro MRI was performed following injection with gadolinium-DTPA-A beta(1-40). Was found that memantine-treated Tg mice performed the same as wild-type control mice, whereas the performance of vehicle-treated Tg mice was significantly impaired (P = 0.0081, one-way ANOVA). Compared with vehicle-treated animals, memantine-treated Tg mice had a reduced plaque burden, as determined both histologically and by micro MRI. This reduction in amyloid burden correlates with an improvement in cognitive performance. Thus, this findings provide further evidence of the potential role of NMDA receptor antagonists in ameliorating AD-related pathology. In addition, our study shows, for the first time, the utility of micro MRI in conjunction with gadolinium-labeled A beta labeling agents to monitor the therapeutic response to amyloid-reducing agents.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
NMDA Receptor

Animal Model

Model Information:
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)
beta Amyloid Deposits
beta Amyloid Load
Activated Astrocytes
Activated Microglia
Dense-core/Compact Plaques
Glial Fibrillary Acidic Protein (GFAP)
Activated Astrocytes
Ex Vivo beta Amyloid Plaque Micro-MRI