Human A beta-amyloid and amyloid precursor protein accumulates in rat brain cells after cultured human leptomeningeal fibroblast implants.
Cultured human leptomeningeal fibroblasts grafted into rat frontal cortex were localized to the implant pocket and to adjacent host leptomeninges. Immunohistochemical studies using a panel of human-specific and domain-specific APP antibodies revealed that all grafted cells expressed both APP and A beta in situ. Remarkably, these antibodies also labeled rat pial and ependymal cells as well as reactive astrocytes adjacent to vessels. In addition, apical projections and cell bodies of many cortical pyramidal neurons contained human-specific APP immunoreactive material. Groups of subcortical neurons, particularly those of the amygdala, hippocampal formation and suprachiasmatic nuclei, were similarly labeled. The presence of human APP in host brains was confirmed by immunoblotting. Birefringent Congo Red staining was observed in the cortical neuropil and in leptomeningeal vessels. These data indicate that grafted leptomeningeal fibroblasts hyperexpress APP and A beta which can diffuse into parenchyma and be taken up by specific rat cells.
DeGiorgio
L A
LA
Will Rogers Institute, Cornell University Medical College, White Plains, NY 10605, USA.
Bernstein
J J
JJ
Manuelidis
L
L
Blass
J P
JP
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001099:Arachnoid / Q000166:cytology*; D001718:Birefringence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D017690:Cell Transplantation; D003224:Congo Red; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D006801:Humans; D015151:Immunoblotting; D010841:Pia Mater / Q000166:cytology*; D051381:Rats; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003224:Congo Red