Memantine improves cognition and reduces Alzheimer's-like neuropathology in transgenic mice

Hilda Martinez-Coria, Kim N. Green, Lauren M. Billings, Masashi Kitazawa, Miriam Albrecht, Gerhard Rammes, Chris G. Parsons, Sandeep Gupta, Pradeep Banerjee, Frank M. LaFerla

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

Memantine is an N-methyl-D-aspartate receptor antagonist that is approved for the treatment of moderate to severe Alzheimer's disease (AD). In this study, three groups of triple-transgenic (3xTg-AD) mice with differing levels of AD-like pathology (6, 9, and 15 months of age) were treated for 3 months with doses of memantine equivalent to those used in humans. After the treatment, memantine-treated mice had restored cognition and significantly reduced the levels of insoluble amyloid-β (Aβ), Aβ dodecamers (Aβ*56), prefibrillar soluble oligomers, and fibrillar oligomers. The effects on pathology were stronger in older, more impaired animals. Memantine treatment also was associated with a decline in the levels of total tau and hyperphosphorylated tau. Finally, memantine pre-incubation prevented Aβ-induced inhibition of long-term potentiation in hippocampal slices of cognitively normal mice. These results suggest that the effects of memantine treatment on AD brain include disease modification and prevention of synaptic dysfunction.

Original languageEnglish
Pages (from-to)870-880
Number of pages11
JournalAmerican Journal of Pathology
Volume176
Issue number2
DOIs
StatePublished - Feb 2010

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