Related Experiment Video
Updated: Feb 22, 2026
Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
Memantine inhibits β-amyloid aggregation and disassembles preformed β-amyloid aggregates
Kaori Takahashi-Ito1, Mitsuhiro Makino1, Keiko Okado2
1Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co. Ltd., Shinagawa-ku, Tokyo 140-8710, Japan.
Abstract:
Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect Aβ aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of Aβ aggregates, including Aβs carrying familial AD mutations, and disaggregated preformed Aβ(1-42) fibrils. These results suggest that the inhibition of Aβ aggregation and induction of Aβ disaggregation may be involved in the mechanisms by which memantine reduces Aβ deposition in the brain.
Insights
Memantine, used for Alzheimer's disease, was found to inhibit the formation and promote the breakdown of harmful amyloid-beta (Aβ) protein aggregates in the brain. This suggests a new mechanism for how memantine may help treat Alzheimer's disease.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Memantine is a medication for Alzheimer's disease (AD).
- Previous studies showed memantine reduces amyloid-beta (Aβ) in AD animal models.
- The exact mechanisms of memantine's effect on Aβ are not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which memantine reduces Aβ levels in the brain.
- To evaluate the effect of memantine on Aβ aggregation and disaggregation.
Main Methods:
- Used thioflavin T assay and transmission electron microscopy to study Aβ aggregation.
- Tested the effect of memantine and amantadine on Aβ(1-42) aggregation.
- Investigated memantine's effect on preformed Aβ fibrils and familial AD mutation-carrying Aβs.
Main Results:
- Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner.
- Amantadine, a similar compound, did not inhibit Aβ aggregation.
- Memantine also inhibited the formation of various Aβ aggregates and disaggregated preformed Aβ fibrils.
Conclusions:
- Memantine directly inhibits Aβ aggregation.
- Memantine can disaggregate preformed Aβ fibrils.
- Inhibition of Aβ aggregation and induction of Aβ disaggregation are potential mechanisms for memantine's therapeutic effects in Alzheimer's disease.
Related Concept Videos
01:22Alzheimer's Disease: Treatment
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
03:03Amyloid Fibrils
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:23Antidepressant Drugs: MAOIs and Other Agents