Skip to main content
U.S. flag

An official website of the United States government

Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer's disease mouse model


Year of Publication:
Contact PI Name:
Stephen M. Strittmatter
Contact PI Affiliation:
Yale University School of Medicine, New Haven, Connecticut, USA
Haakon B. Nygaard, Adam C. Kaufman, Tomoko Sekine-Konno, Linda L. Huh, Hilary Going, Samantha J. Feldman, Mikhail A. Kostylev
Primary Reference (PubMED ID):
Funding Source:
Falk Medical Research Trust
Alzheimer's Association
BrightFocus Foundation
UCB Pharma
National Institutes of Health (NIH)
Study Goal and Principal Findings:

This study aimed at demonstrating the efficacy of two antiepileptic drugs (AEDs)  brivaracetam and ethosuximide in treating impairments in spatial memory in two AD mouse models. Using continuous in vivo electroencephalography (EEG) recording, coupled with spatial memory testing, the authors studied whether epileptiform discharges in transgenic AD mice could be used as a marker of drug efficacy for memory improvement.  The authors report that, in two transgenic mouse models of AD (APP/PS1 and 3xTg-AD), the presence of spike-wave discharges (SWDs) correlated with impairments in spatial memory,although a weaker correlation was seen in 3xTg-AD mice. Both ethosuximide and brivaracetam reduced mouse SWDs, but only brivaracetam reversed memory impairments in APP/PS1 mice. Biochemical and immunohistochemical analyses indicated that epileptiform discharges were not associated with changes in Aβ metabolism or deposition.  Data showed that, similar to levetiracetam, brivaracetam interacts with synapticvesicle protein 2A (SV2A), and confirm that targeting SV2A,  which results in broad-spectrum anticonvulsant action, reverses memory impairments in the APP/PS1 model of AD. Finally, while  SWDs in APP/PS1 mice correlate with impairments in spatial memory, the reduction of these discharges is not a reliable surrogate marker of preclinical drug efficacy in the APP/PS1 AD mouse model.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Synaptic Vesicle Protein 2A (SV2A)
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
T-Type Calcium Channel/CaV3 Channel

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
C57BL/6 x C3H)F2
Model Type:
Strain/Genetic Background:
C57BL/6J × 129/Sv

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
Morris Water Maze
beta Amyloid Load
Brain-beta Amyloid Peptide-Total
Amyloid Precursor Protein (APP) Metabolites
Postsynaptic Density Protein 95 (PSD95)
Electroencephalogram (EEG) Spike Wave Discharge