Reversible memory loss in a mouse transgenic model of Alzheimer's disease

Linda A. Kotilinek, Brian Bacskai, Marcus Westerman, Takeshi Kawarabayashi, Linda Younkin, Bradley T. Hyman, Steven Younkin, Karen H. Ashe

Research output: Contribution to journalArticlepeer-review

376 Scopus citations

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition, believed to be irreversible, characterized by inexorable deterioration of memory and intellect, with neuronal loss accompanying amyloid plaques and neurofibrillary tangles. In an amyloid precursor protein transgenic mouse model, Tg2576, little or no neuronal loss accompanies age-related memory impairment or the accumulation of Aβ, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain Aβ and memory in Tg2576 mice stratified by age (Westerman et al., 2002). Broadening the age range examined obscured this relationship, leading us to propose that small, soluble assemblies of Aβ disrupt cognitive function in these mice. Here we show that memory loss can be fully reversed in Tg2576 mice using intraperitoneally administered BAM-10, a monoclonal antibody recognizing the N terminus of Aβ. The beneficial effect of BAM-10 was not associated with a significant Aβ reduction, but instead eliminated the inverse relationship between brain Aβ and memory. We postulate that BAM-10 acts by neutralizing Aβ assemblies in the brain that impair cognitive function. Our results indicate that a substantial portion of memory loss in Tg2576 mice is not permanent. If these Aβ assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients.

Original languageEnglish (US)
Pages (from-to)6331-6335
Number of pages5
JournalJournal of Neuroscience
Volume22
Issue number15
DOIs
StatePublished - Aug 1 2002

Keywords

  • Alzheimer's disease
  • Behavior
  • Memory
  • Monoclonal antibodies
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Reversible memory loss in a mouse transgenic model of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this