Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles.
Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-beta (Abeta) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Abeta pathology. We describe improved cognitive function following a reduction in both soluble Abeta and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Abeta alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Abeta immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.
Oddo
Salvatore
S
Departments of Neurobiology and Behavior and Neurology, and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697, USA.
Vasilevko
Vitaly
V
Caccamo
Antonella
A
Kitazawa
Masashi
M
Cribbs
David H
DH
LaFerla
Frank M
FM
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D016875:tau Proteins / Q000737:chemistry
D016229:Amyloid beta-Peptides; D016207:Cytokines; D016875:tau Proteins