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

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

190 Zitate (Scopus)

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.

OriginalspracheEnglisch
Seiten (von - bis)870-880
Seitenumfang11
FachzeitschriftAmerican Journal of Pathology
Jahrgang176
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - Feb. 2010

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