RT Journal Article
SR Electronic
T1 Reversible Memory Loss in a Mouse Transgenic Model of Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6331
OP 6335
DO 10.1523/JNEUROSCI.22-15-06331.2002
VO 22
IS 15
A1 Kotilinek, Linda A.
A1 Bacskai, Brian
A1 Westerman, Marcus
A1 Kawarabayashi, Takeshi
A1 Younkin, Linda
A1 Hyman, Bradley T.
A1 Younkin, Steven
A1 Ashe, Karen H.
YR 2002
UL http://www.jneurosci.org/content/22/15/6331.abstract
AB 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.