Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.
X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. AbetaPP-Tg2576 mice produce high levels of brain Abeta and develop age-related defects in memory function that correlate with increasing Abeta load. Overexpression of X11alpha alone had no detectable adverse effect upon behavior. However, X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer's disease.
Mitchell
Jacqueline C
JC
MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK.
Perkinton
Michael S
MS
Yates
Darran M
DM
Lau
Kwok-Fai
KF
Rogelj
Boris
B
Miller
Christopher C J
CC
McLoughlin
Declan M
DM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins