Transplanted astrocytes internalize deposited beta-amyloid peptides in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. The neuropathological hallmarks include extracellular senile plaques consisting of deposited beta-amyloid (Abeta) peptides and intraneuronal neurofibrillary tangles. Neuroinflammation and activation of astrocytes are also well-established features of AD neuropathology; however, the relationships between astrocytes and Abeta deposition remain unclear. Previous studies have shown that adult mouse astrocytes internalize and degrade Abeta deposits in brain sections prepared from human amyloid precursor protein (APP) transgenic mice. In the present study, we demonstrate that cultured adult, but not neonatal mouse astrocytes, respond morphologically and degrade Abeta deposits present in human AD brain. We also transplanted astrocytes isolated from enhanced green fluorescent protein expressing adult and neonatal mice into the hippocampi of human Abeta plaque-bearing transgenic APPSwe+PS1dE9 (APdE9) mice and their wild-type littermates and followed the migration and localization of these astrocytes by confocal microscopy upto 7 days after transplantation. Posttransplantation the astrocytes localized as aggregates or thin strings of many cells within the hippocampi of APdE9 and wild-type mice and showed limited migration from the injection site. Interestingly, most of the transplanted astrocytes were found near Abeta deposits in the hippocampi of APdE9 mice. In contrast to findings in ex vivo degradation assay, confocal microscopy revealed that both adult and neonatal transplanted astrocytes internalized human Abeta immunoreactive material in vivo. These results support the role of astrocytes as active Abeta clearing cells in the CNS that may have important implications for future development of therapeutic strategies for AD.

Pihlaja R ，Koistinaho J ，Malm T ，Sikkilä H ，Vainio S ，Koistinaho M ... -  《GLIA》

Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.

van Groen T ，Kiliaan AJ ，Kadish I 《NEUROBIOLOGY OF DISEASE》

A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition.

Flood DG ，Lin YG ，Lang DM ，Trusko SP ，Hirsch JD ，Savage MJ ，Scott RW ，Howland DS ... -  《-》

Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice.

Malm TM ，Koistinaho M ，Pärepalo M ，Vatanen T ，Ooka A ，Karlsson S ，Koistinaho J ... -  《NEUROBIOLOGY OF DISEASE》

In vivo labelling of hippocampal beta-amyloid in triple-transgenic mice with a fluorescent acetylcholinesterase inhibitor released from nanoparticles.

Härtig W ，Kacza J ，Paulke BR ，Grosche J ，Bauer U ，Hoffmann A ，Elsinghorst PW ，Gütschow M ... -  《-》