Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.
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.
Vodovotz
Y
Y
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lucia
M S
MS
Flanders
K C
KC
Chesler
L
L
Xie
Q W
QW
Smith
T W
TW
Weidner
J
J
Mumford
R
R
Webber
R
R
Nathan
C
C
Roberts
A B
AB
Lippa
C F
CF
Sporn
M B
MB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000302:isolation & purification*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000302:isolation & purification*
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D019001:Nitric Oxide Synthase