RT Journal Article
SR Electronic
T1 β-Amyloid Immunotherapy Prevents Synaptic Degeneration in a Mouse Model of Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9096
OP 9101
DO 10.1523/JNEUROSCI.1697-05.2005
VO 25
IS 40
A1 Buttini, Manuel
A1 Masliah, Eliezer
A1 Barbour, Robin
A1 Grajeda, Henry
A1 Motter, Ruth
A1 Johnson-Wood, Kelly
A1 Khan, Karen
A1 Seubert, Peter
A1 Freedman, Stephen
A1 Schenk, Dale
A1 Games, Dora
YR 2005
UL http://www.jneurosci.org/content/25/40/9096.abstract
AB Alzheimer's disease neuropathology is characterized by key features that include the deposition of the amyloid β peptide (Aβ) into plaques, the formation of neurofibrillary tangles, and the loss of neurons and synapses in specific brain regions. The loss of synapses, and particularly the associated presynaptic vesicle protein synaptophysin in the hippocampus and association cortices, has been widely reported to be one of the most robust correlates of Alzheimer's disease-associated cognitive decline. The β-amyloid hypothesis supports the idea that Aβ is the cause of these pathologies. However, the hypothesis is still controversial, in part because the direct role of Aβ in synaptic degeneration awaits confirmation. In this study, we show that Aβ reduction by active or passive Aβ immunization protects against the progressive loss of synaptophysin in the hippocampal molecular layer and frontal neocortex of a transgenic mouse model of Alzheimer's disease. These results, substantiated by quantitative electron microscopic analysis of synaptic densities, strongly support a direct causative role of Aβ in the synaptic degeneration seen in Alzheimer's disease and strengthen the potential of Aβ immunotherapy as a treatment approach for this disease.