TY - JOUR
T1 - Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease
AU - Vodovotz, Yoram
AU - Lucia, M. Scott
AU - Flanders, Kathleen C.
AU - Chesler, Louis
AU - Xie, Qiao Wen
AU - Smith, Thomas W.
AU - Weidner, Jeffrey
AU - Mumford, Richard
AU - Webber, Robert
AU - Nathan, Carl
AU - Roberts, Anita B.
AU - Lippa, Carol F.
AU - Sporn, Michael B.
PY - 1996/10/1
Y1 - 1996/10/1
N2 - In Alzheimer's disease (AD), affected neurons accumulate β amyloid protein, components of which can induce mouse microglia to express the high- output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice NOS2 is normally suppressed by transforming growth factor β1 (TGF-β1). Expression of TGF-β1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies a previously described polyclonal and two new monoclonal antibodies.Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but expressed in small amounts in 3 control subjects aged 77-78 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.
AB - In Alzheimer's disease (AD), affected neurons accumulate β amyloid protein, components of which can induce mouse microglia to express the high- output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice NOS2 is normally suppressed by transforming growth factor β1 (TGF-β1). Expression of TGF-β1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies a previously described polyclonal and two new monoclonal antibodies.Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but expressed in small amounts in 3 control subjects aged 77-78 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.
UR - http://www.scopus.com/inward/record.url?scp=10244235267&partnerID=8YFLogxK
U2 - 10.1084/jem.184.4.1425
DO - 10.1084/jem.184.4.1425
M3 - Article
C2 - 8879214
AN - SCOPUS:10244235267
SN - 0022-1007
VL - 184
SP - 1425
EP - 1433
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -