title: Absence of Nitric Oxide Synthase 3 Increases Amyloid β-Protein Pathology in Tg-5xFAD Mice.
abstract: OBJECTIVE
  The abnormal accumulation, assembly and deposition of the amyloid β-protein (Aβ) are prominent pathological features of patients with Alzheimer's disease (AD) and related disorders. A number of factors in the brain can influence Aβ accumulation and associated pathologies. The aim of the present study was to determine the consequences of deleting nitric oxide synthase (NOS) 3, the endothelial form of NOS, in Tg-5xFAD mice, a model of parenchymal AD-like amyloid pathology.
  
  
  METHODS
  Tg-5xFAD mice were bred with NOS3-/-mice. Cohorts of Tg-5xFAD mice and bigenic Tg-5xFAD/NOS3-/-mice were aged to six months followed by collection of the blood and brain tissues from the mice for biochemical and pathological analyses.
  
  
  RESULTS
  ELISA analyses show that the absence of NOS3 results in elevated levels of cerebral and plasma Aβ peptides in Tg-5xFAD mice. Immunohistochemical analyses show that the absence of NOS3 increased the amount of parenchymal Aβ deposition and fibrillar amyloid accumulation in Tg-5xFAD mice. The elevated levels of Aβ were not due to changes in the expression levels of transgene encoded human amyloid precursor protein (APP), endogenous β-secretase, or increased proteolytic processing of APP.
  
  
  CONCLUSIONS
  The results from this study suggest that the loss of NOS3 activity enhances Aβ pathology in Tg-5xFAD mice. These findings are similar to previous studies of NOS2 deletion suggesting that reduced NOS activity and NO levels enhance amyloid-associated pathologies in human APP transgenic mice.
authors.affiliation: Departments of Neurosurgery & Medicine, Stony Brook, Stony Brook University, New York, USA.
authors.forename: Zishuo Ian
authors.initials: ZI
authors.lastname: Hu
authors.forename: Ann Marie E
authors.initials: AM
authors.lastname: Kotarba
authors.forename: William E
authors.initials: WE
authors.lastname: Van Nostrand
keywords: Alzheimer’s Disease; Amyloid β-Protein; Deposition; Nitric Oxide Synthase 3; Transgenic Mice