PMID- 8879214 OWN - NLM STAT- MEDLINE DCOM- 19961213 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 184 IP - 4 DP - 1996 Oct 1 TI - Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. PG - 1425-33 AB - In Alzheimer's disease (AD), affected neurons accumulate beta 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 beta 1 (TGF-beta 1). Expression of TGF-beta 1 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 was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD. FAU - Vodovotz, Y AU - Vodovotz Y AD - Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Lucia, M S AU - Lucia MS FAU - Flanders, K C AU - Flanders KC FAU - Chesler, L AU - Chesler L FAU - Xie, Q W AU - Xie QW FAU - Smith, T W AU - Smith TW FAU - Weidner, J AU - Weidner J FAU - Mumford, R AU - Mumford R FAU - Webber, R AU - Webber R FAU - Nathan, C AU - Nathan C FAU - Roberts, A B AU - Roberts AB FAU - Lippa, C F AU - Lippa CF FAU - Sporn, M B AU - Sporn MB LA - eng PT - Journal Article PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antibodies, Monoclonal) RN - 0 (Isoenzymes) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/*enzymology/pathology MH - Amino Acid Sequence MH - Antibodies, Monoclonal MH - Antibody Specificity MH - Brain/*enzymology/pathology MH - Enzyme Induction MH - Female MH - Humans MH - Immunoblotting MH - Immunohistochemistry MH - Isoenzymes/*isolation & purification MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Neurons/*enzymology/pathology MH - Nitric Oxide Synthase/*isolation & purification PMC - PMC2192831 EDAT- 1996/10/01 00:00 MHDA- 1996/10/01 00:01 PMCR- 1997/04/01 CRDT- 1996/10/01 00:00 PHST- 1996/10/01 00:00 [pubmed] PHST- 1996/10/01 00:01 [medline] PHST- 1996/10/01 00:00 [entrez] PHST- 1997/04/01 00:00 [pmc-release] AID - 97033517 [pii] AID - 10.1084/jem.184.4.1425 [doi] PST - ppublish SO - J Exp Med. 1996 Oct 1;184(4):1425-33. doi: 10.1084/jem.184.4.1425.