Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

Yoram Vodovotz; M. Scott Lucia; Kathleen C. Flanders; Louis Chesler; Qiao Wen Xie; Thomas W. Smith; Jeffrey Weidner; Richard Mumford; Robert Webber; Carl Nathan; Anita B. Roberts; Carol F. Lippa; Michael B. Sporn

doi:10.1084/jem.184.4.1425

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

Yoram Vodovotz^*, M. Scott Lucia, Kathleen C. Flanders, Louis Chesler, Qiao Wen Xie, Thomas W. Smith, Jeffrey Weidner, Richard Mumford, Robert Webber, Carl Nathan, Anita B. Roberts, Carol F. Lippa, Michael B. Sporn

^*Corresponding author for this work

Surgery

Research output: Contribution to journal › Article › peer-review

279 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1425-1433
Number of pages	9
Journal	Journal of Experimental Medicine
Volume	184
Issue number	4
DOIs	https://doi.org/10.1084/jem.184.4.1425
State	Published - 1 Oct 1996

Access to Document

10.1084/jem.184.4.1425

Cite this

Vodovotz, Y., Lucia, M. S., Flanders, K. C., Chesler, L., Xie, Q. W., Smith, T. W., Weidner, J., Mumford, R., Webber, R., Nathan, C., Roberts, A. B., Lippa, C. F., & Sporn, M. B. (1996). Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. Journal of Experimental Medicine, 184(4), 1425-1433. https://doi.org/10.1084/jem.184.4.1425

@article{7bb4e9e3edf24ae386a223700c763e9e,

title = "Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease",

abstract = "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.",

author = "Yoram Vodovotz and Lucia, {M. Scott} and Flanders, {Kathleen C.} and Louis Chesler and Xie, {Qiao Wen} and Smith, {Thomas W.} and Jeffrey Weidner and Richard Mumford and Robert Webber and Carl Nathan and Roberts, {Anita B.} and Lippa, {Carol F.} and Sporn, {Michael B.}",

year = "1996",

month = oct,

day = "1",

doi = "10.1084/jem.184.4.1425",

language = "English",

volume = "184",

pages = "1425--1433",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "4",

}

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 -

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

Abstract

Access to Document

Fingerprint

Cite this