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The Journal of Neuroscience, August 1, 2002, 22(15):6331-6335

BRIEF COMMUNICATION
Reversible Memory Loss in a Mouse Transgenic Model of Alzheimer's Disease

Linda A. Kotilinek¹, Brian Bacskai², Marcus Westerman¹, Takeshi Kawarabayashi³, Linda Younkin³, Bradley T. Hyman², Steven Younkin³, and Karen H. Ashe¹

¹ Departments of Neurology and Neuroscience, University of Minnesota, Minneapolis 55455, ² Department of Neurology, Massachusetts General Hospital East, Charlestown, Massachusetts 02129, and ³ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224

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 A, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain A 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 A 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 A. The beneficial effect of BAM-10 was not associated with a significant A reduction, but instead eliminated the inverse relationship between brain A and memory. We postulate that BAM-10 acts by neutralizing A 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 A assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients.

Key words: Alzheimer's disease; transgenic; behavior; A; monoclonal antibodies; memory

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22156331-05$05.00/0

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