Human neurons that constitutively secrete A beta do not induce Alzheimer's disease pathology following transplantation and long-term survival in the rodent brain.
Since cultured neurons secrete beta-amyloid (A beta) peptides, and A beta forms amyloid deposits in the Alzheimer's disease (AD) brain, transplanted neurons may induce the deposition of A beta in the host brain. To assess this possibility, we studied grafted human neurons (NT2N cells) and their progenitors (NT2 cells) in the rodent brain. Although NT2N cells secrete more A beta than the NT2 cells in vitro, no A beta deposits or other AD lesions were induced in the rodent brain by grafts that survived days (NT2 and NT2N cells) to 46 weeks (NT2N cells). Thus, neither the deposition of A beta nor the induction of other AD lesions are obligatory consequences of the transplantation and long-term survival of human neurons or their progenitors in the rodent brain.
Mantione
J R
JR
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Kleppner
S R
SR
Miyazono
M
M
Wertkin
A M
AM
Lee
V M
VM
Trojanowski
J Q
JQ
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002470:Cell Survival; D017690:Cell Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D014183:Transplantation, Heterologous / Q000502:physiology*
D016229:Amyloid beta-Peptides